ORCID Profile
0000-0002-4022-2623
Current Organisation
Griffith University
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Medicinal and Biomolecular Chemistry | Biologically Active Molecules | Biological And Medical Chemistry | Biological Sciences Not Elsewhere Classified | Natural Products Chemistry | Biochemistry And Cell Biology Not Elsewhere Classified | Biochemistry and Cell Biology | Biochemistry and Cell Biology not elsewhere classified | Analytical Spectrometry | Other Biological Sciences | Synthesis Of Macromolecules | Structural Chemistry | Organic Chemical Synthesis | Other Studies in Human Society | Characterisation Of Macromolecules | Nanochemistry and Supramolecular Chemistry | Chemical Characterisation of Materials | Management And Environment | Systems Biology | Studies of Aboriginal and Torres Strait Islander Society | Molecular Evolution | Medicinal and Biomolecular Chemistry not elsewhere classified | Enzymes | Analytical Chemistry | Neurosciences Not Elsewhere Classified | Organic Chemistry | Social and Cultural Anthropology | Biomolecular Modelling and Design | Cheminformatics and Quantitative Structure-Activity Relationships | Biotechnology Not Elsewhere Classified | Physical Chemistry (Incl. Structural) | Soil Chemistry | Cell Development, Proliferation and Death
ANZSRC Socio-Economic Objective (SEO)
Expanding Knowledge in the Chemical Sciences | Expanding Knowledge in the Biological Sciences | Treatments (e.g. chemicals, antibiotics) | Biological sciences | Chemical sciences | Forestry | Other | Flora, Fauna and Biodiversity of environments not elsewhere classified | Horticultural Crops not elsewhere classified | Respiratory system and diseases (incl. asthma) | Health and support services not elsewhere classified | Skeletal system and disorders (incl. arthritis) | Health not elsewhere classified | Diagnostics | Global climate change adaptation measures | Infectious Diseases | Plastics in primary forms | Expanding Knowledge through Studies of Human Society | Infectious diseases | Nervous system and disorders | Higher education | Inherited diseases (incl. gene therapy) | Information Processing Services (incl. Data Entry and Capture) |
Related Links
Publications
4-Amino-2,6-dichloro-5-nitropyrimidine
Publisher: International Union of Crystallography (IUCr)
Date: 23-01-2004
Binding Studies of the Prodrug HAO472 to SARS-Cov-2 Nsp9 and Variants
Publisher: American Chemical Society (ACS)
Date: 15-02-2022
ANTAGONISM BY MANGANESE OF ISOPRENALINE DILATATION OF THE GUINEA‐PIG ISOLATED TRACHEA
Publisher: Wiley
Date: 10-1983
DOI: 10.1111/J.1440-1681.1983.TB00219.X
Abstract: Manganese (0.5-100 mumol/l) was found to be a potent inhibitor of the dilator effect of isoprenaline on the isolated tracheal muscle of the guinea-pig. Above these concentrations the inhibitory action of Mn2+ diminished and no inhibition occurred above 1000 mumol/l Mn2+. Thus a bell-shaped dose-response curve resulted for the inhibition of isoprenaline by Mn2+. The antagonism was surmountable but apparently noncompetitive. Dilation of the isolated trachea caused by theophylline or nitroprusside was not inhibited by Mn2+ at concentrations of 12.5 to 750 mumol/l. At the dose range which could be tested manganese did not antagonize isoprenaline bronchodilatation in vivo. However, manganese at doses between 0.5 and 2.0 mumol/kg inhibited increased in pulmonary resistance caused by acetylcholine, histamine or serotonin. At concentrations above 250 mumol/l Mn2+ inhibited constrictor responses to histamine, acetylcholine and serotonin in guinea-pig isolated ileum and trachea, and inhibited serotonin and prostaglandin E2 contractions in rat fundus. Co2+, Fe2+, Fe3+ and Zn2+ were also tested for their action against isoprenaline on the isolated trachea. Co2+ was similar in effect to Mn2+ but had only 1/50 of the potency. Up to the highest concentrations which could be tested, namely 1000 mumol/l, the other trace metals produced negligible effects. Thus Mn2+ showed selective inhibition of the relaxant effect of isoprenaline on the guinea-pig isolated trachea, at concentrations of Mn2+ well below those shown previously to inhibit constrictor responses by block of transmembrane Ca2+ entry. It is suggested that Mn2+ may interfere with intracellular Ca2+ fluxes in the isolated trachea.
Discovery of tanshinone derivatives with anti-MRSA activity via targeted bio-transformation
Publisher: Elsevier BV
Date: 09-2016
Anthoptilides A−E, New Briarane Diterpenes from the Australian Sea Pen Anthoptilum cf. kukenthali
Publisher: American Chemical Society (ACS)
Date: 03-2000
DOI: 10.1021/NP9903806
Abstract: The Australian sea pen Anthoptilum cf. kukenthali has afforded five new briarane-type diterpenes, anthoptilides A-E. Their structures were determined on the basis of their spectroscopic data. Single-crystal X-ray determination was performed on anthoptilide A. Anthoptilides B and C inhibited the binding of [(3)H]1, 3-dipropyl-8-cyclopentylxanthine ([(3)H]DPCPX) on adenosine A(1) receptors.
Analysis of Approaches to Anti-tuberculosis Compounds
Publisher: American Chemical Society (ACS)
Date: 27-10-2020
Acutangulosides A−F, Monodesmosidic Saponins from the Bark of Barringtonia acutangula
Publisher: American Chemical Society (ACS)
Date: 11-02-2005
DOI: 10.1021/NP049741U
Abstract: Nine triterpene saponins, acutangulosides A-F (2-7), and acutanguloside D-F methyl esters (5a-7a) and a single triterpene aglycone (1) were isolated from a water extract of the bark of Barringtonia acutangula. Their structures were assigned on the basis of spectroscopic data.
Pyrazolo[3,4-d]pyrimidines; adenosine receptor selectivity
Publisher: Elsevier BV
Date: 10-1995
Isolation of Psammaplin A 11‘-Sulfate and Bisaprasin 11‘-Sulfate from the Marine Sponge Aplysinella rhax
Publisher: American Chemical Society (ACS)
Date: 23-02-2000
DOI: 10.1021/NP990335Y
Abstract: Psammaplin A 11'-sulfate (3) and bisaprasin 11'-sulfate (4) have been isolated from the marine sponge Aplysinella rhax, along with the known psammaplin A (1). Their structures were determined on the basis of their spectroscopic data. Compounds 1 and 3 inhibited [(3)H]1,3-dipropyl-8-cyclopentylxanthine binding to rat-brain adenosine A(1) receptors.
Adociasulfate-9, a New Hexaprenoid Hydroquinone from the Great Barrier Reef Sponge Adocia aculeata
Publisher: American Chemical Society (ACS)
Date: 04-11-1999
DOI: 10.1021/NP9902035
Naturally occurring scaffolds for compound library design: convenient access to bis-aryl 1-azaadamantanes carrying a vicinal amino alcohol motif
Publisher: Elsevier BV
Date: 09-2014
Food Allergy Readiness and Anaphylaxis Management in Early Childhood Education and Care in Western Australia
Publisher: SAGE Publications
Date: 12-2018
Abstract: WITH THE INCREASE IN prevalence of food allergy (FA) in young children, early childhood education and care (ECEC) providers are likely to have more enrolments of children who are at risk of anaphylaxis. This study examines the status of FA management in ECEC, and assesses the services’ current readiness to prevent and manage FA. A cross-sectional study comprising an online survey with multiple-choice and open-ended questions was conducted with 53 long day care services in Western Australia. Among the respondents, 83 per cent of services had at least one child enrolled with FA, 96 per cent had an FA policy, and 91 per cent required staff to undertake anaphylaxis training. A high level of self-reported confidence and skills were demonstrated however, gaps were identified in risk-minimisation knowledge, use of adrenaline (epinephrine) autoinjectors and available resources. Extensive promotion of available resources will help improve compliance with anaphylaxis guidelines.
Psammaplysenes C and D, Cytotoxic Alkaloids from Psammoclemma sp.
Publisher: American Chemical Society (ACS)
Date: 11-2007
DOI: 10.1021/NP0703646
Abstract: The sponge Psammoclemma sp. was investigated as part of our studies to discover P2X 7 receptor antagonists for the treatment of inflammatory disease. The biological activity of this extract was found to be due to the cytotoxicity of two new bromotyrosine alkaloids, psammaplysenes C (1) and D (2), and not P2X 7-specific activity. Their structures were determined by 1D and 2D NMR spectroscopy.
Merosesquiterpene Congeners from the Australian Sponge Hyrtios digitatus as Potential Drug Leads for Atherosclerosis Disease
Publisher: MDPI AG
Date: 27-12-2017
DOI: 10.3390/MD15010006
Natural products and the search for novel vaccine adjuvants
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.VACCINE.2011.07.041
Abstract: Vaccines that protect against intracellular infections such as malaria, Leishmania and Chlamydia require strong cellular responses based on CD4(+) T cells and CD8(+) T cells in addition to antibodies. Such cell-mediated responses can be potentiated with adjuvants. However, very few adjuvants have been licensed for use in humans thus there is an urgent need for the discovery of new non-toxic adjuvants in order to produce more efficacious vaccines. Until recently, the mechanisms of how adjuvants worked remained largely unknown, but, it is becoming clearer that many function via host germline-encoded pattern recognition receptors (PRRs) expressed by most immune and non-immune cells. Most PRRs sense infection and transmit a series of signals that ultimately lead to the development of immunity. PRR mediated signalling can be harnessed to search for new vaccine adjuvants. Dendritic cells (DCs) express many PRRs and are remarkably effective at directing T cell immunity. Natural products (NPs) have been the basis of many drugs and are a rich source of immune activators and/or regulators of the immune response. Here we review PRRs in the context of NPs and propose the use of DCs as biological probes to help identify novel immune type molecules and adjuvants within collections of NPs.
SYNTHESIS OF 5-AMINOPYRAZOLE-4-CARBONITRILES
Publisher: CSIRO Publishing
Date: 1989
DOI: 10.1071/CH9890747
Abstract: A one-pot reaction between substituted hydrazines, malononitrile and triethyl orthoformate leads directly to the formation of 1-substituted 5-aminopyrazole-4-carbonitriles. The scope and limitations of this synthetic procedure are discussed in relation to the well established synthesis of these compounds via substituted hydrazines and ethoxymethylenemalononitrile.
Dereplication Strategies for Targeted Isolation of New Antitrypanosomal Actinosporins A and B from a Marine Sponge Associated-Actinokineospora sp. EG49
Publisher: MDPI AG
Date: 06-03-2014
DOI: 10.3390/MD12031220
Styracifoline from the Vietnamese Plant Desmodium styracifolium: A Potential Inhibitor of Diabetes-Related and Thrombosis-Based Proteins
Publisher: American Chemical Society (ACS)
Date: 09-2021
Aplysinopsin, a new tryptophan derivative from a sponge
Publisher: Elsevier BV
Date: 1977
Spongian Diterpenes with Thyrotropin Releasing Hormone Receptor 2 Binding Affinity from Spongia sp.
Publisher: American Chemical Society (ACS)
Date: 12-04-2008
DOI: 10.1021/NP070658R
Abstract: High-throughput screening of a plant and marine invertebrate extract library to find natural products with rat thyrotropin releasing hormorne (TRH) receptor 2 binding affinity led to the isolation of four new (1-4) and one known (5) spongian diterpene from the sponge Spongia sp. The structures were assigned from interpretation of 2D NMR and high-resolution ESIMS data. The absolute configurations of 1-4 were proposed on the basis of analysis of their CD spectra. Diterpenes 1-5 showed rat TRH receptor 2 binding affinity with IC(50) values of 23 microM, 70 microM, 400 microM, 600 microM, and 1 mM, respectively.
Anti-staphylococcal activity of C-methyl flavanones from propolis of Australian stingless bees (Tetragonula carbonaria) and fruit resins of Corymbia torelliana (Myrtaceae)
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.FITOTE.2014.03.024
Abstract: Propolis of Australian stingless bees (Tetragonula carbonaria, Meliponini) originating from Corymbia torelliana (Myrtaceae) fruit resins was tested for its antimicrobial activities as well as its flavonoid contents. This study aimed at the isolation, structural elucidation and antibacterial testing of flavanones of C. torelliana fruit resins that are incorporated into stingless bee propolis. Flavanones of this study were elucidated by spectroscopic and spectrometric methods including UV, 1D and 2D NMR, EI-MS, ESI-MS and HR-MS. The results indicated known C-methylated flavanones namely, 1 (2S)-cryptostrobin, its regioisomer 2 (2S)- stroboponin, 3 (2S)- cryptostrobin 7-methyl ether, and 6 (2S)- desmethoxymatteucinol, and known flavanones 4 (2S)- pinostrobin and 5 (2S)- pinocembrin as markers for C. torelliana fruit resins and one propolis type. Ethanolic preparations of propolis were shown to be active against Staphylococcus aureus (ATCC 25923) and to a lesser extent against Pseudomonas aeruginosa (ATCC 27853). C. torelliana flavanones inhibited the growth of S. aureus therefore contributing to the antibacterial effects observed for Australian stingless bee propolis extracts.
Direct Screening of Natural Product Extracts Using Mass Spectrometry
Publisher: Elsevier BV
Date: 04-2008
Abstract: The authors describe first a proof-of-concept experiment to show direct affinity screening using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) is a rapid and informative approach for natural product extract screening. The study used 10 alkaloid-enriched plant extracts and 8 desalted marine extracts spiked with specific inhibitors of bovine carbonic anhydrase II (bCAII EC4.2.1.1) as a model set. The spiked extracts were incubated with bCAII and then analyzed by ESI-FTICR-MS. The noncovalent complexes were detected, and the specific inhibitors were reidentified in the spiked natural product extracts. There was no interference from the desalted/alkaloid-enriched extracts to the formation of the noncovalent complexes. The method allowed quick identification of the molecular mass of the bound ligand. The authors then applied the screening to identify active compounds in natural product extracts. They employed direct infusion and online size exclusion chromatography (SEC) ESI-FTICR-MS to detect intact target-ligand complex. Eighty-five methanolic plant extracts were screened against bCAII by direct infusion ESI-FTICR-MS and by online SEC-ESI-FTICR-MS. One noncovalent complex was identified from the same plant extract by both methods. The molecular weight of the bound ligand from this extract was determined. Mass-directed purification gave 6-(1S-hydroxy-3-methylbutyl)-7-methoxy-2H-chromen-2-one (1) as the active compound. Subsequently, the binding to bCAII was confirmed by ESI-FTICR-MS. The binding specificity was determined by competition experiments between 1 and furosemide, a specific ligand of bCAII.
New Lamellarin Alkaloids from the Australian Ascidian, Didemnum chartaceum
Publisher: American Chemical Society (ACS)
Date: 26-01-1999
DOI: 10.1021/NP9803530
Similar interactions of natural products with biosynthetic enzymes and therapeutic targets could explain why nature produces such a large proportion of existing drugs
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C1NP00026H
LAT Transport Inhibitors from Pittosporum venulosum Identified by NMR Fingerprint Analysis
Publisher: American Chemical Society (ACS)
Date: 18-05-2015
DOI: 10.1021/NP500968T
Abstract: (1)H NMR fingerprints were used as the guiding principle for the isolation of minor compounds related to the l-type amino acid transporter inhibitors venulosides A (1) and B (2). Two new monoterpene glycosides, namely, venulosides C (3) and D (4), were isolated from a Queensland collection of the plant Pittosporum venulosum. Compounds 3 and 4 were found to inhibit l-leucine transport in LNCaP cells with IC50 values of 11.47 and 39.73 μM, respectively. The venulosides are the first reported natural product inhibitors of leucine transport in prostate cancer cells, and the isolation of the minor compounds provides some early SAR information.
New laurene derivatives from Laurencia filiformis
Publisher: CSIRO Publishing
Date: 1976
DOI: 10.1071/CH9762533
Abstract: Three new compounds containing the laurene skeleton are reported from the red alga Laurencia filiformis f. heteroclada.
<title>Visualization tool for simulating ligand-receptor binding process</title>
Publisher: SPIE
Date: 08-03-1996
DOI: 10.1117/12.234676
Cytotoxic agarofurans from the seeds of the Australian rainforest vine Celastrus subspicata
Publisher: Elsevier BV
Date: 11-2009
Bioinspiration from Marine Scaffolds
Publisher: Wiley
Date: 19-03-2018
Testicular Caspase-3 and β-Catenin Regulators Predicted via Comparative Metabolomics and Docking Studies
Publisher: MDPI AG
Date: 11-01-2020
Abstract: Many routes have been explored to search for effective, safe, and affordable alternatives to hazardous female contraceptives. Herbal extracts and their secondary metabolites are some of the interesting research areas to address this growing issue. This study aims to investigate the effects of ten different plant extracts on testicular spermatogenesis. The correlation between the chemical profile of these extracts and their in vivo effect on male reproductive system was evaluated using various techniques. Approximately 10% of LD50 of hydro-methanolic extracts were orally administrated to rats for 60 days. Semen parameters, sexual organ weights, and serum levels of male sex hormones in addition to testes histopathology, were evaluated. Moreover, metabolomic analysis using (LC-HRESIMS), multivariate analysis (PCA), immunohistochemistry (caspase-3 and β-catenin), and a docking study were performed. Results indicated that three plant extracts significantly decreased epididymal sperm density and motility. Moreover, their effects on testicular cells were also assured by histopathological evaluations. Metabolomic profiling of the bioactive plant extracts showed the presence of erse phytochemicals, mostly oleanane saponins, phenolic diterpenes, and lupane triterpenes. A docking study on caspase-3 enzyme showed that oleanane saponins possessed the highest binding affinity. An immunohistochemistry assay on β-catenin and caspase-3 indicated that Albizzia lebbeck was the most active extract for decreasing immunoexpression of β-catenin, while Rosmarinus officinalis showed the highest activity for increasing immunoexpression of caspase-3. The spermatogenesis decreasing the activity of A. lebbeck, Anagallis arvensis, and R. officinalis can be mediated via up-regulation of caspase-3 and down-regulation of β-catenin existing in testis cells.
Synthesis and adenosine receptor affinity of a series of pyrazolo[3,4-d]pyrimidine analogues of 1-methylisoguanosine
Publisher: American Chemical Society (ACS)
Date: 09-1991
DOI: 10.1021/JM00113A031
Abstract: Pyrazolo[3,4-d]pyrimidines are pyrazolo analogues of purines. They have been shown to be a general class of compounds which exhibit A1 adenosine receptor affinity. Two series of pyrazolo[3,4-d]pyrimidine analogues of 1-methylisoguanosine have been synthesized. The first involved substitution of the N1-position while the second involved substitution of the N5-position. Both alkyl and aryl substituents were examined. All compounds were tested for A1 adenosine receptor affinity by using a (R)-[3H]-N6-(phenylisopropyl)adenosine binding assay. The 3-chlorophenyl group showed the greatest activity in the N1-position and the butyl group produced the greatest activity in the N5-position. Combination of the best substituent in each of these positions enhanced the overall activity. The most potent compound was 4-amino-5-N-butyl-1-(3-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-6(5H)- one with an IC50 of 6.4 x 10(-6) M. Selectivity at the receptor subclasses was examined by performing an A2 adenosine receptor affinity assay with [3H]CGS 21680. This series of compounds were slightly less potent at A2 receptors. 4-Amino-5-N-butyl-1-(3-chlorophenyl-1H-pyrazolo[3,4-d]pyrimidin-6(5H)-one was the most potent compound with an IC50 of 19.2 x 10(-6) M.
Adenosine receptors as potential therapeutic targets
Publisher: Elsevier BV
Date: 12-1999
DOI: 10.1016/S1359-6446(99)01421-X
Abstract: Recent studies indicate a widening role for adenosine receptors in many therapeutic areas. Adenosine receptors are involved in immunological and inflammatory responses, respiratory regulation, the cardiovascular system, the kidney, various CNS-mediated events including sleep and neuroprotection, as well as central and peripheral pain processes. In this review, the physiological role of adenosine receptors in these key areas is described with reference to the therapeutic potential of adenosine receptor agonists and antagonists.
Evaluation of fermentation conditions triggering increased antibacterial activity from a near-shore marine intertidal environment-associated Streptomyces species
Publisher: Elsevier BV
Date: 03-2017
Synthesis of melicodenines C, D and E
Publisher: Elsevier BV
Date: 12-2012
Two Novel Bisalkylated Norscalaranes From the Sponge Carteriospongia foliascens
Publisher: CSIRO Publishing
Date: 1989
DOI: 10.1071/CH9890751
Abstract: Two novel 20,24-dimethyl-25-norscalaranes have been isolated from the hexane extract of Carteriospongia foliascens and their structures determined by a combination of 1H and 13C n.m.r. spectroscopy and e.i . mass spectrometry.
Critical micelle concentration and hemolytic activity — a correlation suggested by the marine sterol, halistanol trisulfate
Publisher: Elsevier BV
Date: 1992
DOI: 10.1016/S0006-291X(05)80119-6
Abstract: The marine natural product, halistanol trisulfate, has a relatively low critical micelle concentration of 0.001% m/v (14.5 microM) and strong hemolytic potency with an EC50 of 0.00046% m/v (6.67 microM). As expected of a detergent, it inhibits the growth of gram-positive but not gram-negative bacteria. The hemolytic activity of halistanol trisulfate and other detergents has been shown to correlate with critical micelle concentration. This correlation may have important implications in the mechanism of membranolytic bioactivity.
Parkinson's disease: Alterations in iron and redox biology as a key to unlock therapeutic strategies
Publisher: Elsevier BV
Date: 05-2021
Identification of a New α-Synuclein Aggregation Inhibitor via Mass Spectrometry Based Screening
Publisher: American Chemical Society (ACS)
Date: 22-05-2019
DOI: 10.1021/ACSCHEMNEURO.9B00092
Abstract: The aggregation of disordered α-synuclein protein is pathogenically connected with Parkinson's disease. Therefore, discovering molecules that can inhibit the misfolding and aggregation of α-synuclein is an active research area in PD drug development. A key property of such required therapeutic agents is specific binding to the target protein. Mass spectrometry allows rapid detection of direct interactions between molecules and proteins and is an ideal technique for discovering specific α-synuclein binders. Here, by setting up an automated mass spectrometry-based screening system, we were able to screen over 2500 compounds and identify a new α-synuclein inhibitor, 3-[(3-methoxyphenyl)carbamoyl]-7-[( E)-2-phenylethenyl]-4,7-dihydropyrazolo [1,5- a]pyrimidine-5-carboxylic acid (compound 2). This compound not only significantly inhibits the misfolding and aggregation of α-synuclein and protects neuroblastoma cells from α-synuclein toxicity, but also has a more specific binding site compared with positive controls. Our work for the first time reports the inhibition of compound 2 on α-synuclein aggregation and also consolidates the capability of mass spectrometry to discover α-synuclein aggregation inhibitors.
Amberlite XAD-7 as a Chromatographic Absorbent
Publisher: Oxford University Press (OUP)
Date: 10-1982
Inhibition of protein phosphatase 2A by cantharidin analogues
Publisher: Elsevier BV
Date: 05-1996
Cardenolide Glycosides from Elaeodendron australe var. integrifolium
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.PHYTOCHEM.2013.11.024
Abstract: Extracts from dried leaf and stems of Elaeodendron australe var. integrifolium (Celastraceae) collected in South East Queensland, Australia, were active in an assay that measured Ca(2+) driven expression of IL-2/luciferase designed to identify inhibitors of the ICRAC channel. Bioassay-guided isolation using C18 and polyamide column chromatography, HPLC (Phenyl and C18) and centrifugal partition chromatography (CPC) led to the isolation of digitoxigenin (1) and three cardenolide glycosides, glucoside 2, quinovoside 3 and the new natural product xyloside 4, as the active components with low nM activity in the reporter assay.
Marine Actinomycetes in Biodiscovery
Publisher: Springer Berlin Heidelberg
Date: 2015
10-hydroxydarlingine, a new tropane alkaloid from the Australian proteaceous plant Triunia erythrocarpa
Publisher: American Chemical Society (ACS)
Date: 24-03-2000
DOI: 10.1021/NP9906065
Abstract: Triunia erythrocarpa was identified as containing alkaloids during chemical screening of Queensland Proteaceae using Dragendorff's reagent. A new tropane, 10-hydroxydarlingine (1), and the known tropane, darlingine (2), were isolated from the leaves of T. erythrocarpa. The absolute stereochemistry of 10-hydroxydarlingine (1) was assigned using the advanced Mosher method. T. erythrocarpa is only the seventh member of the Proteaceae to have been shown to produce alkaloids.
High-pressure synthesis of enantiomerically pure C-6 substituted pyrazolo[3,4-d] pyrimidines
Publisher: Elsevier BV
Date: 2001
DOI: 10.1016/S0960-894X(00)00620-X
Abstract: The synthesis of enantiomerically pure C-6 substituted pyrazolo[3,4-d]pyrimidines has been performed by aromatic nucleophilic substitution of 4-amino-6-chloro-1-phenylpyrazolo[3,4-rd]pyrimidine under conditions of high pressure at ambient temperature. Conventional synthetic conditions (reflux at atmospheric pressure) were unsuccessful. The S enantiomer 11 displayed higher affinity and selectivity for the adenosine A1 receptor than the R enantiomer 12.
Reversible depigmentation of human melanoma cells by halistanol trisulphate, a novel marine sterol
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 1992
DOI: 10.1097/00008390-199201000-00006
Abstract: The pigmented human melanoma cell line, MM418, became demelanized when treated continuously with a nontoxic level of halistanol trisulphate (HTS), a C29 steroidal detergent isolated from a marine sponge. Nontoxic levels of halistanol or of a range of anionic, cationic and neutral detergents had no such effect. Control MM418 cells varied greatly in size, appearance and pigmentation HTS-treated cells were smaller than controls, had a uniform, generally bipolar appearance, and lacked pigment. HTS induced only minor changes in cell ultrastructure, with fewer mature melanosomes being found in treated cells. Suppression of melanin synthesis was apparent within 24 h of addition of HTS, as judged by inhibited incorporation of the false precursor, 5[125I]-2-thiouracil. Reversal of inhibition occurred within the same period after removal of HTS. Tyrosinase activity gradually decreased to 25% of the control value during a 19-day treatment with HTS, and expression of two carbohydrate-dependent tyrosinase epitopes, 5C12 and 2B7, was abolished. Expression of one other melanosomal protein and of vimentin was not affected. The results suggest that HTS inhibits maturation of tyrosinase to a form associated with melanin synthesis.
Phospholipase A2 in Cnidaria
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.CBPC.2004.09.006
Abstract: Phospholipase A2 (PLA2) is an enzyme present in snake and other venoms and body fluids. We measured PLA2 catalytic activity in tissue homogenates of 22 species representing the classes Anthozoa, Hydrozoa, Scyphozoa and Cubozoa of the phylum Cnidaria. High PLA2 levels were found in the hydrozoan fire coral Millepora sp. (median 735 U/g protein) and the stony coral Pocillopora damicornis (693 U/g) that cause skin irritation upon contact. High levels of PLA2 activity were also found in the acontia of the sea anemone Adamsia carciniopados (293 U/g). Acontia are long threads containing nematocysts and are used in defense and aggression by the animal. Tentacles of scyphozoan and cubozoan species had high PLA2 activity levels: those of the multitentacled box jellyfish Chironex fleckeri contained 184 U/g PLA2 activity. The functions of cnidarian PLA2 may include roles in the capture and digestion of prey and defense of the animal. The current observations support the idea that cnidarian PLA2 may participate in the sting site irritation and systemic envenomation syndrome resulting from contact with cnidarians.
Longithorols C−E. Three New Macrocyclic Sesquiterpene Hydroquinone Metabolites from the Australian Ascidian, Aplidium longithorax
Publisher: American Chemical Society (ACS)
Date: 16-09-1999
DOI: 10.1021/NP990217A
Abstract: Chemical investigation of a Great Barrier Reef ascidian, Aplidium longithorax has resulted in the isolation of two new para-substituted cyclofarnesylated hydroquinone compounds, longithorols C (1) and D (2), and a novel macrocyclic chromenol, longithorol E (3). Longithorol C (1) had its absolute stereochemistry determined by the advanced Mosher method and all compounds had their structures determined by interpretation of spectroscopic data.
Nature Bank and the Queensland Compound Library: Unique International Resources at the Eskitis Institute for Drug Discovery
Publisher: Bentham Science Publishers Ltd.
Date: 31-03-2014
DOI: 10.2174/1386207317666140109120515
Abstract: The Eskitis Institute for Drug Discovery is home to two unique resources, Nature Bank and the Queensland Compound Library (QCL), that differentiate it from many other academic institutes pursuing chemical biology or early phase drug discovery. Nature Bank is a comprehensive collection of plants and marine invertebrates that have been subjected to a process which aligns downstream extracts and fractions with lead- and drug-like physicochemical properties. Considerable expertise in screening natural product extracts/fractions was developed at Eskitis over the last two decades. Importantly, biodiscovery activities have been conducted from the beginning in accordance with the UN Convention on Biological Diversity (CBD) to ensure compliance with all international and national legislative requirements. The QCL is a compound management and logistics facility that was established from public funds to augment previous investments in high throughput and phenotypic screening in the region. A unique intellectual property (IP) model has been developed in the case of the QCL to stimulate applied, basic and translational research in the chemical and life sciences by industry, non-profit, and academic organizations.
An alternative computer model of the 3-dimensional structural of microcystin-LR and nodularin rationalising their interactions with protein phosphatases 1 and 2A
Publisher: Elsevier BV
Date: 1992
Tyrosyl-DNA Phosphodiesterase I Inhibitors from the Australian Plant Macropteranthes leichhardtii
Publisher: American Chemical Society (ACS)
Date: 07-07-2015
DOI: 10.1021/ACS.JNATPROD.5B00211
Abstract: Mass-directed isolation of the CH2Cl2/MeOH extract from the bark of an Australian plant, Macropteranthes leichhardtii, resulted in the purification of a new phenylpropanoid glucoside, macropteranthol (1), together with four known analogues (2-5). The structure of compound 1 was elucidated by NMR and MS data analyses and quantum chemical calculations. Compounds 3 and 5 showed inhibitory activity against tyrosyl-DNA phosphodiesterase I with IC50 values of ∼1.0 μM.
Synthesis of Four Novel Natural Product Inspired Scaffolds for Drug Discovery
Publisher: American Chemical Society (ACS)
Date: 23-12-2009
DOI: 10.1021/JO802456W
Abstract: Inspired by the novel spiro structures of a number of bioactive natural products such as the histrionicotoxins, a series of novel spiro scaffolds have been designed and robust syntheses developed. The scaffolds are ready-to-use building blocks and can be easily prepared on a 5-20 g scale. They contain two amino groups (one Boc-protected) and have been designed for ease of conversion to a lead generation library, using either amide formation or reductive amination procedures. The synthesis of the 1,9-diazaspiro[5.5]undecane and 3,7-diazaspiro[5.6]dodecane ring systems was achieved using RCM as the key step. A simple workup procedure is reported for the removal of highly colored ruthenium residues. The synthesis of the 1,8-diazaspiro[4.5]decane scaffold has been achieved using a bromine-mediated 5-endo cyclization of the corresponding 4-aminobutene intermediate under acidic conditions. This is the first ex le of this type of cyclization to be reported. A novel mechanism involving a bromine transfer reaction from an initially formed bromonium ion to a neighboring nitrogen atom is suggested as the reason for the failure of this type of reaction under "normal" bromination conditions. An unusual rearrangement of a 1-acyl-1,9-diazaspiro[5.5]undecane to the corresponding 9-acyl-1,9-diazaspiro[5.5]undecane is reported.
Polydiscamides B−D from a Marine Sponge Ircinia sp. as Potent Human Sensory Neuron-Specific G Protein Coupled Receptor Agonists
Publisher: American Chemical Society (ACS)
Date: 29-12-2007
DOI: 10.1021/NP070094R
Abstract: Polydiscamides B, C, and D (1-3) were isolated from a sponge Ircinia sp. The structures of 1 to 3 were elucidated by the comparison of their NMR and HRESIMS spectroscopic data with that of a structurally related compound, polydiscamide A. All compounds showed potent agonist activity against human sensory neuron-specific G protein couple receptor (SNSR), a receptor involved in the modulation of pain, and they are the first ex les of nonendogenous human SNSR agonists.
The fatty acid synthase inhibitor triclosan: repurposing an antimicrobial agent for targeting prostate cancer
Publisher: Impact Journals, LLC
Date: 03-09-2014
NMR spectral assignments of a new chlorotryptamine alkaloid and its analogues fromAcacia confusa
Publisher: Wiley
Date: 2007
DOI: 10.1002/MRC.1959
Abstract: A new chlorotryptamine alkaloid, N-chloromethyl-N,N-dimethyltryptamine, was isolated from a methanol extract of the Chinese shrub Acacia confusa Merr., together with its known hallucinogenic analogues, N-methyltryptamine, N,N-dimethyltryptamine and N,N-dimethyltryptamine-N-oxide. The new compound was an artefact of the isolation conditions. The complete (1)H and (13)C NMR assignments for these compounds were carried out using (1)H, (13)C, DEPT, gCOSY, gHSQC and gHMBC NMR experiments.
A Modular Approach to Assembly of Totally Synthetic Self-adjuvanting Lipopeptide-based Vaccines Allows Conformational Epitope Building
Publisher: Elsevier BV
Date: 04-2011
Anti-mycobacterial natural products and mechanisms of action
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D1NP00011J
Abstract: This review summarises the molecular targets of 53 anti-TB natural products and highlights the compounds with novel targets and activity against drug-resistant TB.
Biologically active isoquinoline alkaloids with drug-like properties from the genus Corydalis
Publisher: Royal Society of Chemistry (RSC)
Date: 28-03-2014
DOI: 10.1039/C3RA47944G
Botryllamides K and L, new tyrosine derivatives from the Australian ascidian Aplidium altarium
Publisher: Elsevier BV
Date: 06-2010
Turning Metabolomics into Drug Discovery
Publisher: Sociedade Brasileira de Quimica (SBQ)
Date: 2016
Isolation of xestosterol esters of brominated acetylenic fatty acids from the marine sponge Xestospongia testudinaria
Publisher: American Chemical Society (ACS)
Date: 11-09-1999
DOI: 10.1021/NP9901635
Abstract: The CH(2)Cl(2) extract of the marine sponge Xestospongia testudinaria inhibited [(3)H]DPCPX binding to rat-brain adenosine A(1) receptors. Bioassay-guided fractionation led to the isolation of a known brominated acetylenic fatty acid 1 as the active component. Also isolated were two novel sterol esters 2 and 3. All structures were determined on the basis of their spectroscopic data.
Synthesis of cis-Bicyclo[4,4,0]deca-2,8-dien-4-one
Publisher: CSIRO Publishing
Date: 1973
DOI: 10.1071/CH9730595
Abstract: A synthesis of cis-bicyclo[4,4,0]deca-2,8-dien-4-one is described, starting from the Diels-Alder adduct of methoxybenzo-1,4-quinone and 1,3-butadiene.
Isomers of a marine diterpene distinguish sublines of human melanoma cells on the basis of apoptosis, cell cycle arrest and differentiation markers
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 1992
DOI: 10.1097/00008390-199201000-00007
Abstract: The action of the marine furanoditerpenes, spongiatriol (SP) and episopongiatriol (ESP), were compared in two sublines of human melanoma cells (MM96E and MM96L) derived from the same metastatic lesion. MM96E had higher tyrosinase activity and lower expression of alkaline phosphatase but was otherwise indistinguishable from MM96L. SP and ESP treatment of both cell lines for 72 h at cytostatic doses inhibited B8G3 expression and tyrosinase activity but had little effect on the expression of tyrosinase antigen. MM96L cells were affected more than MM96E. SP and ESP induced apoptosis in both cell lines, ESP causing dendritic morphology in a proportion of MM96L cells. SP induced a marked G2/M arrest in MM96E cells. SP and ESP together define subtle qualitative and quantitative differences in human melanoma phenoypes, possibly based on expression of a repertoire of neurotransmitter receptors.
R-(–)-β-O-methylsynephrine, a natural product, inhibits VEGF-induced angiogenesis in vitro and in vivo
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.BBRC.2010.07.025
Abstract: R-(-)-beta-O-methylsynephrine (OMe-Syn) is an active compound isolated from a plant of the Rutaceae family. We conducted cell proliferation assays on various cell lines and found that OMe-Syn more strongly inhibited the growth of human umbilical vein endothelial cells (HUVECs) than that of other normal and cancer cell lines tested. In angiogenesis assays, it inhibited vascular endothelial growth factor (VEGF)-induced invasion and tube formation of HUVECs with no toxicity. The anti-angiogenic activity of OMe-Syn was also validated in vivo using the chorioallantonic membrane (CAM) assay in growing chick embryos. Expression of the growth factors VEGF, hepatocyte growth factor, and basic fibroblast growth factor was suppressed by OMe-Syn in a dose-dependent manner. Taken together, our results indicate that this compound could be a novel basis for a small molecule targeting angiogenesis.
Thrombin Inhibitors from the Freshwater Cyanobacterium Anabaena compacta
Publisher: American Chemical Society (ACS)
Date: 05-09-2012
DOI: 10.1021/NP300282A
Abstract: Bioassay-guided investigation of the cyanobacterium Anabaena compacta extracts afforded spumigin J (1) and the known thrombin inhibitor spumigin A (2). The absolute configuration of 1 was analyzed by advanced Marfey's methodology. Compounds 1 and 2 inhibited thrombin with EC(50) values of 4.9 and 2.1 μM, and 0.7 and 0.2 μM in the cathepsin B inhibitory assay, respectively. The MM-GBSA methodology predicted spumigin A with 2S-4-methylproline as the better thrombin inhibitor.
Trikentramides A-D, Indole Alkaloids from the Australian Sponge Trikentrion flabelliforme
Publisher: American Chemical Society (ACS)
Date: 04-11-2013
DOI: 10.1021/NP400617H
Abstract: Chemical investigations of two specimens of Trikentrion flabelliforme collected from Australian waters have resulted in the identification of four new indole alkaloids, trikentramides A-D (9-12). The planar chemical structures for 9-12 were established following analysis of 1D/2D NMR and MS data. The relative configurations for 9-12 were determined following the comparison of (1)H NMR data with data previously reported for related natural products. The application of a quantum mechanical modeling method, density functional theory, confirmed the relative configurations and also validated the downfield carbon chemical shift observed for one of the quaternary carbons (C-5a) in the cyclopenta[g]indole series. The indole-2,3-dione motif present in trikentramides A-C is rare in nature, and this is the first report of these oxidized indole derivatives from a marine sponge.
Guiding principles for natural product drug discovery
Publisher: Future Science Ltd
Date: 06-2012
DOI: 10.4155/FMC.12.55
Abstract: Natural products (NPs) have historically been a fertile source of new drugs for the pharmaceutical industry. However, this once-popular approach has waned considerably over the past two decades as the high-throughput screening of megalibraries comprised mainly of molecules with non-natural (synthetic) motifs has unfolded. Contemporary high-throughput screening libraries contain molecules compliant with physicochemical profiles considered essential for downstream development. Until recently, there was no strategy that aligned NP screening with the same physicochemical profiles. An approach based on Log P has addressed these concerns and, together with advances in isolation, afforded NP leads in timelines compatible with pure compound screening. Concomitant progress related to access of biological resources has provided long-awaited legal certainty to further facilitate NP drug discovery.
Developing a Drug-like Natural Product Library
Publisher: American Chemical Society (ACS)
Date: 08-02-2008
DOI: 10.1021/NP070526Y
Lysianadioic acid, a carboxypeptidase B inhibitor from Lysiana subfalcata
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.BMCL.2007.12.060
Abstract: A new natural product, lysianadioic acid, was isolated from the plant Lysiana subfalcata as a carboxypeptidase B (CPB) inhibitor. It is a potent inhibitor of CPB with an IC(50) of 0.36 microM. This is the first known ex le of a small molecule CPB inhibitor isolated from plant origin. Its structure was determined by NMR spectroscopy.
Production of Induced Secondary Metabolites by a Co-Culture of Sponge-Associated Actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163
Publisher: MDPI AG
Date: 22-05-2014
DOI: 10.3390/MD12053046
Predicting natural product value, an exploration of anti-TB drug space
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4NP00021H
Abstract: Here we present a perspective based on an analysis of the drug-like properties of the reported anti-mycobacterium natural products in order to assess drug potential.
(−)-Dibromophakellin: An α2B adrenoceptor agonist isolated from the Australian marine sponge, Acanthella costata
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.BMC.2009.01.065
Abstract: Bioassay-guided fractionation of the organic extract from the marine sponge Acanthella costata resulted in the isolation of the known natural product, (-)-dibromophakellin (1). Using a fluorescence imaging plate reader (FLIPR) based assay, compound 1 was identified as displaying agonist activity against the alpha(2B) adrenoceptor, with an EC(50) of 4.2muM. Debromination and Suzuki-Miyaura coupling reactions were undertaken in order to provide structure activity data about the pyrrole ring of this marine metabolite. These synthetic studies generated the known natural product analogues, (-)-phakellin (2), and (-)-monobromophakellin (3), along with the new synthetic derivatives (-)-4-bromo-5-phenylphakellin (5) and (-)-4,5-diphenylphakellin (6). Substitution of the C-5 Br of 1 with H (2 and 3) or phenyl (5 and 6) resulted in loss of activity indicating that Br at C-5 is required for agonist activity.
Scaffold Flatness: Reversing the Trend
Publisher: Springer Science and Business Media LLC
Date: 23-10-2013
Anhydride modified cantharidin analogues. Is ring opening important in the inhibition of protein phosphatase 2A?
Publisher: Elsevier BV
Date: 10-2000
DOI: 10.1016/S0223-5234(00)00186-0
Abstract: A series of anhydride modified cantharidin analogues have been synthesised and screened for their ability to inhibit protein phosphatase 2A. Surprisingly only analogues capable of undergoing a facile ring opening of the anhydride moiety displayed any significant inhibition. Subsequent NMR experiments indicated that 7-oxobicyclo[2.2.1]heptane-2,3-dicarboxylic acid was the major (sole) species under assay conditions. The ability of these modified anhydro-cantharidin analogues to inhibit protein phosphatase 2A varies from 4 (16) to 100% (8) at 100 microM test concentration.
Harnessing the Properties of Natural Products
Publisher: Annual Reviews
Date: 06-01-2018
DOI: 10.1146/ANNUREV-PHARMTOX-010716-105029
Abstract: Natural products (NPs) have been used as traditional medicines since antiquity. With more than 10 60 estimated compounds with molecular weights less than 500 Da representing chemical space, NPs occupy a very small percentage however, they are significantly overrepresented in biologically relevant chemical space. The classical approach concentrates on identifying one or more NPs with biological activity from a source organism. There is much more to be learned from NPs than we can discover this narrow view. In this review, we discuss ways to harness the global properties of NPs.
Chemical investigation of an antimalarial Chinese medicinal herb Picrorhiza scrophulariiflora
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.BMCL.2013.08.077
Abstract: An antimalarial medicinal plant Picrorhiza scrophulariiflora was chemically investigated as part of our ongoing research in traditional chinese medicines (TCM). Mass directed fractionation of the active part of the crude extract led to the isolation of ten main components, three new compounds (1-3) and seven known compounds (4-10). Compound 10 inhibited the growth of the Plasmodium falciparum 3D7 malarial parasite line, with an IC50 value of 8.3μM. This compound accounted for ∼95% of P. falciparum growth inhibitory activity in the crude extract confirming, for this TCM, that a single compound was responsible for the antimalarial activity.
Polyoxygenated Dysidea sterols that inhibit the binding of [I125] IL-8 to the human recombinant IL-8 receptor type A
Publisher: American Chemical Society (ACS)
Date: 24-03-2000
DOI: 10.1021/NP9904657
Abstract: The combined CH(2)Cl(2) and MeOH crude extract of a new species of the marine sponge Dysidea, collected in Northern Australia was found to inhibit the binding of [I125] interleukin-8 [IL-8] to the human recombinant IL-8 receptor type A at 500 microg/mL. Bioassay-guided fractionation led to the isolation of three new polyoxygenated sterols 3, 4, and 5. Their structures were assigned on the basis of 1D and 2D NMR experiments, and relative stereochemistries were established by ROESY correlations and analysis of coupling constants. The IC(50) values for inhibition of IL-8Ra for sterols 3, 4, and 5 were 20, 5.5, and 4.5 microM, respectively.
Tyrosine kinase inhibitors from the rainforest tree Polyscias murrayi
Publisher: Elsevier BV
Date: 02-2005
DOI: 10.1016/J.PHYTOCHEM.2004.12.022
Abstract: A series of 3-(4-hydroxyphenyl) propanoic acid derivatives, which inhibit Itk (interleukin-2 inducible T-cell kinase), a Th2-cell target, were isolated from the Australian rainforest tree Polyscias murrayi. The new compound 3-(4-hydroxyphenyl) propionyl choline and a 2:1 mixture of the new compounds 3,4-di-O-3-(4-hydroxyphenyl) propionyl-1,5-dihydroxycyclohexanecarboxylic acid and 3,5-di-O-3-(4-hydroxyphenyl) propionyl-1,4-dihydroxycyclohexanecarboxylic acid were isolated along with two known compounds 3-(4-hydroxyphenyl) propanoic acid and 3-(3,4-hydroxyphenyl) propanoic acid. Their structures were determined by 1D and 2D NMR spectroscopy. The assay results suggest that both the 3-(4-hydroxyphenyl) propanoate and carboxyl moieties contribute to Itk activity of the compounds.
Isolation of symbiotic dinoflagellates by centrifugal elutriation1
Publisher: Wiley
Date: 1986
A Common Protein Fold Topology Shared by Flavonoid Biosynthetic Enzymes and Therapeutic Targets
Publisher: American Chemical Society (ACS)
Date: 30-12-2005
DOI: 10.1021/NP050229Y
Abstract: The relationship between a natural product's biosynthetic enzyme and its therapeutic target is unknown. The concept of protein fold topologies, as a determining factor in recognition, has been developed through molecular modeling techniques. We have shown that biosynthetic enzymes and the therapeutic targets of three classes of natural products that inhibit protein kinases share a common protein fold topology (PFT) and cavity recognition points despite having different fold type classifications. The clinical agent flavopiridol would have been identified by this new approach.
Synthesis of novel molecular probes inspired by harringtonolide
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C1OB05299C
Abstract: A novel harringtonolide-inspired scaffold containing a cycloheptatriene ring and two fused cyclopentane rings has been synthesised from simple starting materials. The scaffold, containing a similar substitution pattern and relative stereochemistry to the complex diterpenoid, has been enumerated into a small library of derivatives. One of these library members has been converted into a sub-library of substituted triazoles using copper-catalysed azide-alkyne cycloaddition (click) chemistry. The scaffold may be useful in drug discovery or in the preparation of additional molecular probes for chemical biology.
Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond
Publisher: Public Library of Science (PLoS)
Date: 28-07-2016
Native Mass Spectrometry for the study of PROTAC GNE-987-containing ternary complexes.
Publisher: Wiley
Date: 04-05-2021
Abstract: PRO teolysis TA rgeting C himeras (PROTACs) promote the degradation, rather than inhibition, of a drug target as a mechanism for therapeutic treatment. Bifunctional PROTAC molecules allow simultaneous binding of both the target protein and an E3‐Ubiquitin ligase, bringing the two proteins into close spatial proximity to allow ubiquitinylation and degradation of the target protein via the cell's endogenous protein degradation pathway. We utilized native mass spectrometry (MS) to study the ternary complexes promoted by the previously reported PROTAC GNE‐987 between Brd4 bromodomains 1 and 2, and Von Hippel Lindeau E3‐Ubiquitin Ligase. Native MS at high resolution allowed us to measure ternary complex formation as a function of PROTAC concentration to provide a measure of complex affinity and stability, whilst simultaneously measuring other intermediate protein species. Native MS provides a high‐throughput, low s le consumption, direct screening method to measure ternary complexes for PROTAC development.
Adenosine receptors: new opportunities for future drugs
Publisher: Elsevier BV
Date: 06-1998
DOI: 10.1016/S0968-0896(98)00038-8
Abstract: This review summarises current knowledge on adenosine receptors, an important G protein-coupled receptor. The four known adenosine receptor subtypes A1, A2A, A2B, and A3 are discussed with special reference to the opportunities for drug development.
13C n.m.r. spin–lattice relaxation time measurements determining the major tautomer of 1-methylisoguanosine in solution
Publisher: Royal Society of Chemistry (RSC)
Date: 1980
DOI: 10.1039/C39800000339
Zwitterionic 2-(methylamino)ethanesulfonic acid
Publisher: International Union of Crystallography (IUCr)
Date: 30-04-2003
Endophytic Streptomyces sp. Y3111 from traditional Chinese medicine produced antitubercular pluramycins
Publisher: Springer Science and Business Media LLC
Date: 05-11-2013
DOI: 10.1007/S00253-013-5335-6
Abstract: As part of a search for antitubercular substances from natural sources, we screened a library of endophytic microbes (50 strains and 300 crude extracts in total) isolated from traditional Chinese medicines (TCMs) for growth inhibitory activity against Bacillus Calmette-Guérin (BCG). The crude extract of Streptomyces sp. strain Y3111, which was associated with the stems of Heracleum souliei, showed good anti-BCG activity with an MIC value of 12.5 μg/mL. Bioassay-guided isolation led to four new pluramycin-type compounds, heraclemycins A-D (1-4). Their structures were determined by different spectroscopic techniques including HRMSESI, 1D NMR, and 2D NMR. This is the first report of pluramycin analogues produced by TCM endophytic microbes as well as the first ex le of BCG-selective pluramycins. Heraclemycin C (3) showed selective antitubercular activity against BCG with a MIC value of 6.25 μg/mL and a potential new mode of action.
Tetradehydrofurospongin-1, a new C-21 furanoterpene from a sponge
Publisher: Elsevier BV
Date: 04-1976
Antimalarial Activity of Pyrroloiminoquinones from the Australian Marine Sponge Zyzzya sp
Publisher: American Chemical Society (ACS)
Date: 20-06-2012
DOI: 10.1021/JM3002795
Abstract: A new bispyrroloiminoquinone alkaloid, tsitsikammamine C (1), displayed potent in vitro antimalarial activity with IC(50) values of 13 and 18 nM against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum, respectively. Tsitsikammamine C (1) displayed selectivity indices of >200 against HEK293 cells and inhibited both ring and trophozoite stages of the malaria parasite life cycle. Previously reported compounds makaluvamines J (2), G (3), L (4), K (5) and damirones A (6) and B (7) were also isolated from the same marine sponge (Zyzzya sp.). Compounds 2-4 displayed potent growth inhibitory activity (IC(50) < 100 nM) against both P. falciparum lines and only moderate cytotoxicity against HEK293 cells (IC(50) = 1-4 μM). Makaluvamine G (3) was not toxic to mice and suppressed parasite growth in P. berghei infected mice following subcutaneous administration at 8 mg kg(-1) day(-1).
Synthesis of two chiral octahydroindole scaffolds for drug discovery
Publisher: Elsevier BV
Date: 03-2016
Revised structure of palau’amine
Publisher: Elsevier BV
Date: 06-2007
In silico Driven Pharmacognosy: Forth, Back and Reverse
Publisher: Georg Thieme Verlag KG
Date: 04-05-2015
Flinderoles A−C: Antimalarial Bis-indole Alkaloids from Flindersia Species
Publisher: American Chemical Society (ACS)
Date: 17-12-2008
DOI: 10.1021/OL802506N
Abstract: With the aim of finding new natural product antimalarials, the novel indole alkaloids flinderole A-C were found to have selective antimalarial activities with IC(50) values between 0.15-1.42 microM. Flinderole A was isolated from the Australian plant Flindersia acuminata and flinderoles B and C from the Papua New Guinean plant F. amboinensis. Flinderoles A-C contain an unprecedented rearranged skeleton compared to their related isomers of the borreverine class of compounds.
Clavatadine A, A Natural Product with Selective Recognition and Irreversible Inhibition of Factor XIa
Publisher: American Chemical Society (ACS)
Date: 30-05-2008
DOI: 10.1021/JM800314B
Abstract: Bioassay-guided fractionation of a CH2Cl2/MeOH extract of the sponge Suberea clavata using the serine protease factor XIa to detect antithrombotic activity led to the isolation of the new marine natural products, clavatadines A and B. Clavatadines A and B inhibited factor XIa with IC50's of 1.3 and 27 microM, respectively. A crystal structure of protein-inhibitor (clavatadine A) complex was obtained and revealed interesting selective binding and irreversible inhibition of factor XIa. The cocrystal structure provides guidance for the design and synthesis of future factor XIa inhibitors as antithrombotic agents.
Elicitation of secondary metabolism in actinomycetes
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.BIOTECHADV.2015.06.003
Abstract: Genomic sequence data have revealed the presence of a large fraction of putatively silent biosynthetic gene clusters in the genomes of actinomycetes that encode for secondary metabolites, which are not detected under standard fermentation conditions. This review focuses on the effects of biological (co-cultivation), chemical, as well as molecular elicitation on secondary metabolism in actinomycetes. Our review covers the literature until June 2014 and exemplifies the ersity of natural products that have been recovered by such approaches from the phylum Actinobacteria.
Thiaplakortones A–D: Antimalarial Thiazine Alkaloids from the Australian Marine Sponge Plakortis lita
Publisher: American Chemical Society (ACS)
Date: 25-09-2013
DOI: 10.1021/JO400988Y
Abstract: A high-throughput screening c aign using a prefractionated natural product library and an in vitro antimalarial assay identified active fractions derived from the Australian marine sponge Plakortis lita . Bioassay-guided fractionation of the CH2Cl2/CH3OH extract from P. lita resulted in the purification of four novel thiazine-derived alkaloids, thiaplakortones A-D (1-4). The chemical structures of 1-4 were determined following analysis of 1D/2D NMR and MS data. Comparison of the chiro-optical data for 3 and 4 with literature values of related N-methyltryptophan natural products was used to determine the absolute configuration for both thiaplakortones C and D as 11S. Compounds 1-4 displayed significant growth inhibition against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum (IC50 values 3.9 μM). Thiaplakortone A (1) was the most active natural product, with IC50 values of 51 and 6.6 nM against 3D7 and Dd2 lines, respectively.
The Small Molecule R-(-)-β-O-Methylsynephrine Binds to Nucleoporin 153 kDa and Inhibits Angiogenesis
Publisher: Ivyspring International Publisher
Date: 2015
DOI: 10.7150/IJBS.10603
Antitrypanosomal Cyclic Polyketide Peroxides from the Australian Marine Sponge Plakortis sp.
Publisher: American Chemical Society (ACS)
Date: 17-03-2010
DOI: 10.1021/NP900535Z
Abstract: Bioassay-guided fractionation of the crude extract from the Australian marine sponge Plakortis sp. led to the isolation of two new cyclic polyketide peroxides, 11,12-didehydro-13-oxo-plakortide Q (1) and 10-carboxy-11,12,13,14-tetranor-plakortide Q (2). Antitrypanosomal studies showed that compound 1 had an IC(50) value of 49 nM against Trypanosoma brucei brucei, and compound 2, where a carboxylic acid is present in the side chain, had a 20-fold reduction of activity. 11,12-Didehydro-13-oxo-plakortide Q (1) is the most active peroxide isolated so far against T. b. brucei, and it indicates the potential therapeutic value of this class of compounds.
Niphatoxin C, a Cytotoxic Tripyridine Alkaloid from Callyspongia sp.
Publisher: American Chemical Society (ACS)
Date: 21-11-2007
DOI: 10.1021/NP070366Q
Abstract: As part of our studies to discover P2X 7 receptor antagonists, the sponge Callyspongia sp. was investigated. A new tripyridine alkaloid niphatoxin C ( 1) was isolated and had P2X 7 receptor antagonism however, cytotoxicity of THP-1 cells was the predominant biological effect at higher concentrations. Its structure was determined by 1- and 2-D NMR spectroscopy.
The Time and Place for Nature in Drug Discovery
Publisher: American Chemical Society (ACS)
Date: 14-10-2022
The Resveratrol Tetramer (-)-Hopeaphenol Inhibits Type III Secretion in the Gram-Negative Pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa
Publisher: Public Library of Science (PLoS)
Date: 04-12-2013
Vanillic Acid Derivatives from the Green Algae Cladophora socialis As Potent Protein Tyrosine Phosphatase 1B Inhibitors
Publisher: American Chemical Society (ACS)
Date: 20-10-2007
DOI: 10.1021/NP070225O
Abstract: A novel vanillic acid derivative (1) and its sulfate adduct (2) were isolated from a green algae, Cladophora socialis. The structures of 1 and 2 were elucidated from NMR and HRESIMS experiments. Both compounds showed potent inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), an enzyme involved in the regulation of insulin cell signaling. Compounds 1 and 2 had IC50 values of 3.7 and 1.7 microM, respectively.
NMR Fingerprints of the Drug-like Natural-Product Space Identify Iotrochotazine A: A Chemical Probe to Study Parkinson's Disease
Publisher: Wiley
Date: 15-04-2014
Alkaloids from the Chinese vine gnetum montanum
Publisher: American Chemical Society (ACS)
Date: 31-10-2011
DOI: 10.1021/NP200700F
Abstract: During a high-throughput screening c aign of a prefractionated natural product library, fractions from the Chinese vine Gnetum montanum showed in vitro activity against Pseudomonas aeruginosa wild-type strain, PAO1. UV-directed isolation of the organic extract from the vine leaves resulted in the purification of the new natural products N-methyllaudanosolinium trifluoroacetate (1), 3'-hydroxy-N,N-dimethylcoclaurinium trifluoroacetate (2), 1,9,10-trihydroxy-2-methoxy-6-methylaporphinium trifluoroacetate (3), and 6a,7-didehydro-1,9,10-trihydroxy-2-methoxy-6-methylaporphinium trifluoroacetate (4). Compound 4 is described here for the first time, and this is the first report of compounds 1-3 as natural products. Compounds 1-3 were found to racemize over time. Starting from commercially available (+)-boldine, through a series of semisynthetic reactions, a mechanism for the racemization of the isolated compounds is proposed. The known natural products (-)-latifolian A (5) and magnocurarine (6) were also isolated during these studies. The antibacterial activity was explained by the presence of 5, which displayed an IC50 value of 9.8 μM (MIC = 35 μM).
Biodiversity 'hotspots', patterns of richness and endemism, and taxonomic affinities of tropical Australian sponges (Porifera)
Publisher: Springer Science and Business Media LLC
Date: 2002
Identification of Protein Fold Topology Shared between Different Folds Inhibited by Natural Products
Publisher: Wiley
Date: 24-04-2007
Abstract: Natural products have withstood the test of time as therapeutics, but new lead-generation strategies have focussed away from natural products. A new approach that uses natural-product recognition to drive an understanding of biological space might provide an impetus for renewed focus on natural-product starting points. Protein fold topology (PFT) has been shown to be an underlying factor for natural-product recognition. An investigation of natural product inhibitors of the Zincin-like fold has demonstrated their capacity also to inhibit targets of different fold types. Analysis of crystal structure complexes for natural products cocrystallised within different fold types has shown similarity at the PFT level. Two new PFT(T) (where subscript T denotes PFT shared between therapeutic targets) relationships have been established: the Zincin-like- metallohydrolase/oxidoreductase PFT(T) and the Zincin-like-phosphorylase/hydrolase PFT(T). The PFT relationship between a natural product's biosynthetic enzyme and therapeutic target, and now between different fold targets of the same natural product, suggests that PFT is the simplest descriptor of biological space. This fundamental factor for recognition could facilitate a rational approach to drug development guided by natural products.
Lessons from exploring chemical space and chemical diversity of propolis components
Publisher: MDPI AG
Date: 15-07-2020
DOI: 10.3390/IJMS21144988
Abstract: Propolis is a natural resinous material produced by bees and has been used in folk medicines since ancient times. Due to it possessing a broad spectrum of biological activities, it has gained significant scientific and commercial interest over the last two decades. As a result of searching 122 publications reported up to the end of 2019, we assembled a unique compound database consisting of 578 components isolated from both honey bee propolis and stingless bee propolis, and analyzed the chemical space and chemical ersity of these compounds. The results demonstrated that both honey bee propolis and stingless bee propolis are valuable sources for pharmaceutical and nutraceutical development.
5,6,7,3′,4′,5′-Hexamethoxyflavone from the Australian plant Eremophila debilis (Myoporaceae)
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.FITOTE.2017.07.014
Abstract: The aerial parts of the endemic Australian plant Eremophila debilis (Myoporaceae) contain 3% dry weight of the biologically active 5,6,7,3',4',5'-hexamethoxyflavone, which had its structured confirmed using X-ray crystal crystallography. The presence of significant levels of the polypharmacologically active 5,6,7,3',4',5'-hexamethoxyflavone in the edible parts of the plant has potential implications for its use as a food and bush medicine.
A natural product compound inhibits coronaviral replication in vitro by binding to the conserved Nsp9 SARS-CoV-2 protein
Publisher: Elsevier BV
Date: 12-2021
Lepadins F−H, New cis-Decahydroquinoline Alkaloids from the Australian Ascidian Aplidium tabascum
Publisher: American Chemical Society (ACS)
Date: 21-02-2002
DOI: 10.1021/NP010407X
Abstract: Chemical investigation of a Great Barrier Reef ascidian, Aplidium tabascum, has resulted in the isolation of three new cis-decahydroquinoline alkaloids, lepadins F-H (4-6). The three new compounds differ from the previously isolated lepadins A-C (1-3) in that they contain a fully saturated 5-hydroxyoctyl side chain attached at C-5, an unsaturated eight-carbon ester moiety attached to C-3, and opposite stereochemistry at C-5 and C-3. Lepadins G (5) and H (6) are epimers at C-2. NMR and molecular modeling studies indicated that the three new compounds adopt a chair-chair conformation in which the nitrogen equatorially substitutes the cyclohexyl ring. This contrasts with lepadins A-C (1-3), which adopt a chair-chair conformation in which the nitrogen axially substitutes the cyclohexyl ring.
Phospholipase A2 in porifera
Publisher: Elsevier BV
Date: 03-2004
Diimidazo[1,2-c:4′,5′-e]pyrimidines: N6-N1 conformationally restricted adenosines
Publisher: Elsevier BV
Date: 03-1998
DOI: 10.1016/S0960-894X(98)00101-2
Abstract: Tethering the N6-substituents of N6-substituted adenosines to N1 has resulted in a series of conformationally restricted adenosine analogues. The resultant diimidazo[1,2-c:4',5'-e]pyrimidines were shown to be adenosine A1 selective.
A Computer Generated Model of Adenosine Receptors Rationalising Binding and Selectivity of Receptor Ligands
Publisher: Informa UK Limited
Date: 07-1991
A model to predict anti-tuberculosis activity: value proposition for marine microorganisms
Publisher: Springer Science and Business Media LLC
Date: 13-07-2016
DOI: 10.1038/JA.2016.87
Bioaffinity Mass Spectrometry Screening
Publisher: Elsevier BV
Date: 02-2016
Abstract: Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS or ESI-FTMS) was used to screen 192 natural product extracts and a 659-member natural product-based fragment library for bindings to a potential malaria drug target, Plasmodium falciparum Rab11a (PfRab11a, PF13_0119). One natural product extract and 11 fragments showed binding activity. A new natural product, arborside E, was identified from the active extract of Psydrax montigena as a weak binder. Its binding activity and inhibitory activity against PfRab11a were confirmed by ESI-FTMS titration experiments and an orthogonal enzyme assay.
Low-dose curcumin stimulates proliferation, migration and phagocytic activity of olfactory ensheathing cells.
Publisher: Public Library of Science (PLoS)
Date: 31-10-2014
Native Mass Spectrometry in Fragment-Based Drug Discovery
Publisher: MDPI AG
Date: 28-07-2016
Hepatitis C Virus NS3 Protease and Helicase Inhibitors from Red Sea Sponge (Amphimedon) Species in Green Synthesized Silver Nanoparticles Assisted by in Silico Modeling and Metabolic Profiling
Publisher: Informa UK Limited
Date: 05-2020
DOI: 10.2147/IJN.S233766
Kororamide B, a brominated alkaloid from the bryozoan Amathia tortuosa and its effects on Parkinson's disease cells
Publisher: Elsevier BV
Date: 10-2015
A note of caution in the use of receptor binding assays to screen marine organisms: the action of halistanol trisulphate on adenosine receptors.
Publisher: Elsevier BV
Date: 12-1992
Synthesis and Structure−Activity Relationship of Pyrazolo[3,4-d]pyrimidines: Potent and Selective Adenosine A1 Receptor Antagonists
Publisher: American Chemical Society (ACS)
Date: 1996
DOI: 10.1021/JM960052S
Capturing Nature's Diversity
Publisher: Public Library of Science (PLoS)
Date: 22-04-2015
NMR fingerprints, an integrated approach to uncover the unique components of the drug-like natural product metabolome of termite gut-associated Streptomyces species
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5RA17553D
Abstract: A new NMR-based method to access to the unique components of the drug-like natural product metabolome of termite-gut associated Streptomyces strains has been developed.
A New Quinoline Epoxide from the Australian PlantDrummondita calida
Publisher: Georg Thieme Verlag KG
Date: 06-04-2011
Abstract: A drug discovery program aimed at identifying new antimalarial leads from a prefractionated natural product library has resulted in the purification of a new quinoline alkaloid, (2' R)-2',3'-epoxy- N-methylatanine (1), along with eight known natural products, skimmianin, γ-fagarine, maculosidine, evolitrine, dictamnine, pteleine, N-methylatanine, and werneria chromene. Compound 1 displayed 74 % inhibition at 80 µM against a chloroquine -resistant Plasmodium falciparum strain (Dd2).
Prunolides A, B, and C: Novel Tetraphenolic Bis-Spiroketals from the Australian Ascidian Synoicum prunum
Publisher: American Chemical Society (ACS)
Date: 26-03-1999
DOI: 10.1021/JO981881J
Abstract: Three novel tetraphenolic bis-spiroketals, prunolides A-C (1, 3, and 4) have been isolated from the Australian ascidian Synoicum prunum. The structures were determined from NMR spectroscopic data and from an X-ray analysis of prunolide A. The prunolides contain a unique 1,6,8-trioxadispiro[4.1.4.2]trideca-3,10,12-triene-2,9-dione carbon skeleton. The known compound rubrolide A (5) was also isolated.
Iotrochamides A and B, antitrypanosomal compounds from the Australian marine sponge Iotrochota sp
Publisher: Elsevier BV
Date: 07-2012
DOI: 10.1016/J.BMCL.2012.05.029
Abstract: Bioassay-guided isolation of the CH(2)Cl(2)/MeOH extract from the Australian sponge Iotrochota sp. resulted in the purification of two new N-cinnamoyl-amino acids, iotrochamides A (1) and B (2). The chemical structures of 1 and 2 were determined by 1D/2D NMR and MS data analyses. Compounds 1 and 2 were shown to inhibit Trypanosoma brucei brucei with IC(50) values of 3.4 and 4.7 μM, respectively.
Traditional Chinese medicine extraction method by ethanol delivers drug-like molecules
Publisher: Elsevier BV
Date: 09-2019
Potential of marine natural products against drug-resistant fungal, viral, and parasitic infections
Publisher: Elsevier BV
Date: 02-2017
Endiandrin A, a Potent Glucocorticoid Receptor Binder Isolated from the Australian Plant Endiandra anthropophagorum
Publisher: American Chemical Society (ACS)
Date: 21-06-2007
DOI: 10.1021/NP070073X
Abstract: Bioassay-guided fractionation of the DCM extract from the roots of Endiandra anthropophagorum resulted in the isolation of a new cyclobutane lignan, endiandrin A (1), together with the known natural products nectandrin B (2) and (-)-dihydroguaiaretic acid (3). The structure of 1 was determined by extensive 1D and 2D NMR and MS data analyses. Acetylation and methylation of 1 yielded di-O-acetylendiandrin A (4) and di-O-methylendiandrin A (5), respectively. All compounds were tested in a glucocorticoid receptor binding assay and displayed IC50 values ranging from 0.9 to 35 microM.
SYNTHESIS OF 2-SUBSTITUTED PYRAZOLO[3,4-D]PYRIMIDINES
Publisher: CSIRO Publishing
Date: 1991
DOI: 10.1071/CH9911795
Abstract: The reaction of 1-acetyl-2-phenylhydrazine with ethoxymethylenemalononitrile yielded [(4-cyano-1-phenylpyrazol-3-yl)aminomethylene]propanedinitrile. Hydrolysis followed by annulation with methyl isocyanate provided a synthetic route to 2-phenylpyrazolo[3,4-d]pyrimidines.
Potent Cytotoxic Peptides from the Australian Marine Sponge Pipestela candelabra
Publisher: MDPI AG
Date: 04-06-2014
DOI: 10.3390/MD12063399
The synthesis of a combinatorial library using a tambjamine natural product template
Publisher: CSIRO Publishing
Date: 2001
DOI: 10.1071/CH01123
Diimidazo[1,2-c : 4 ',5 '-e]pyrimidines: Adenosine agonist activity demonstrated by microphysiometry
Publisher: Elsevier BV
Date: 03-1998
DOI: 10.1016/S0960-894X(98)00102-4
Abstract: Silicon-based microphysiometry, measuring extracellular acidification rate of cells in culture, demonstrated that a series of diimidazo[1,2-c:4',5'-e]pyrimidines were agonists at the human adenosine A1 receptor. 5-amino-7,8-dihydro-3-ribofuranose-8-(R)-(phenyl)-3H-diimidazo [1,2-c:4',5'-e]pyrimidine (2a) had an EC50 of 100 microM and reached 90% of the Emax produced by R-PIA.
Adlumiceine methyl ester, a new alkaloid from Fumaria vaillantii
Publisher: Informa UK Limited
Date: 31-10-2014
DOI: 10.1080/10286020.2014.969717
Abstract: A new alkaloid, adlumiceine methyl ester (1), together with two known alkaloids, parfumine (2) and N-methylhydrastine methyl ester (3), was isolated from aerial parts of Fumaria vaillantii. The structures of compounds were determined by 1D/2D NMR and MS data. All three compounds were tested for cytotoxic activity against PC3 and MCF7 cell lines using Alamar blue assay. The tested compounds showed no significant cytotoxic activity (IC50>50 μM) against PC3 and MCF7 cell lines.
A Grand Challenge. 2. Phenotypic Profiling of a Natural Product Library on Parkinson's Patient-Derived Cells
Publisher: American Chemical Society (ACS)
Date: 22-07-2016
DOI: 10.1021/ACS.JNATPROD.6B00258
Abstract: Harnessing the inherent biological relevance of natural products requires a method for the recognition of biological effects that may subsequently lead to the discovery of particular targets. An unbiased multidimensional profiling method was used to examine the activities of natural products on primary cells derived from a Parkinson's disease patient. The biological signature of 482 natural products was examined using multiparametric analysis to investigate known cellular pathways and organelles implicated in Parkinson's disease such as mitochondria, lysosomes, endosomes, apoptosis, and autophagy. By targeting several cell components simultaneously the chance of finding a phenotype was increased. The phenotypes were then clustered using an uncentered correlation. The multidimensional phenotypic screening showed that all natural products, in our screening set, were biologically relevant compounds as determined by an observed phenotypic effect. Multidimensional phenotypic screening can predict the cellular function and subcellular site of activity of new compounds, while the cluster analysis provides correlation with compounds with known mechanisms of action. This study reinforces the value of natural products as biologically relevant compounds.
Chemical Constituents of Kino Extract from Corymbia torelliana
Publisher: MDPI AG
Date: 04-11-2014
An explanation of the substituent effect of 1,3,8-trisubstituted xanthines on adenosine A1/A2 affinity.
Publisher: Elsevier BV
Date: 10-1992
4-Amino-2-chloro-5-nitro-6-(propylamino)pyrimidine
Publisher: International Union of Crystallography (IUCr)
Date: 26-06-2004
Chemistry of Aqueous Marine Extracts: Isolation Techniques
Publisher: Springer Berlin Heidelberg
Date: 1988
The occurrence of 5-hydroxytryptamine in the holothurian,Pentacter crassa
Publisher: Springer Science and Business Media LLC
Date: 09-1981
DOI: 10.1007/BF01971759
Chemical investigation of drug-like compounds from the Australian tree, Neolitsea dealbata
Publisher: Elsevier BV
Date: 10-2010
DOI: 10.1016/J.BMCL.2010.07.100
Abstract: Two of the four parameters in the 'rule of five', molecular weight and logP, which can be detected and predicted by mass spectrometry and compound retention on reversed-phase HPLC, were used as guidelines in natural product isolation. A new aporphine alkaloid, (6aR)-normecambroline (1), was isolated from the bark of Neolitsea dealbata (R. Br.) Merr. Its structure was determined on the basis of NMR, MS and CD analysis. It is the first time the absolute configuration of the roemerine-N-oxide was assigned for both roemerine-N(α)-oxide (3) and roemerine-N(β)-oxide (4). Physico-chemical property evaluation demonstrated all alkaloids had no Lipinski violation. Compound 1 inhibited selectively against cervical cancer cells (HeLa) with an IC(50) of 4.0 μM.
Genome- and MS-based mining of antibacterial chlorinated chromones and xanthones from the phytopathogenic fungus Bipolaris sorokiniana strain 11134
Publisher: Springer Science and Business Media LLC
Date: 19-04-2019
DOI: 10.1007/S00253-019-09821-Z
Abstract: Halogen substituents are important for biological activity in many compounds. Genome-based mining of halogenase along with its biosynthetic gene cluster provided an efficient approach for the discovery of naturally occurring organohalogen compounds. Analysis of the genome sequence of a phytopathogenic fungus Bipolaris sorokiniana 11134 revealed a polyketide gene cluster adjacent to a flavin-dependent halogenase capable of encoding halogenated polyketides, which are rarely reported in phytopathogenic fungi. Furthermore, MS- and UV-guided isolation and purification led to the identification of five chlorine-containing natural products together with seven other chromones and xanthones. Two of the chlorinated compounds and four chromones are new compounds. Their structures were elucidated by NMR spectroscopic analysis and HRESIMS data. The biosynthetic gene clusters of isolated compounds and their putative biosynthetic pathway are also proposed. One new chlorinated compound showed activity against Staphylococcus aureus, methicillin-resistant S. aureus, and three clinical-resistant S. aureus strains with a shared minimum inhibitory concentration (MIC) of 12.5 μg/mL. Genome-based mining of halogenases combined with high-resolution MS- and UV-guided identification provides an efficient approach to discover new halogenated natural products from microorganisms.
Fragment-based screening with natural products for novel anti-parasitic disease drug discovery
Publisher: Informa UK Limited
Date: 12-09-2019
Cyclopentylamine substituted triazolo[4,5-d]pyrimidine: implications for binding to the adenosine receptor
Publisher: Elsevier BV
Date: 07-1991
Inhibition of protein phosphatase 2A by cyclic peptides modelled on the microcystin ring
Publisher: Elsevier BV
Date: 09-1996
Fungal biotransformation of tanshinone results in [4+2] cycloaddition with sorbicillinol: evidence for enzyme catalysis and increased antibacterial activity
Publisher: Springer Science and Business Media LLC
Date: 20-05-2016
DOI: 10.1007/S00253-016-7488-6
Abstract: The biotransformation of tanshinone IIA to a new antibacterial agent tanshisorbicin (1) by the fungus Hypocrea sp. (AS 3.17108) is described. The structure of tanshisorbicin is a hybrid of tanshinone IIA (2) and sorbicillinol (3). The latter is a metabolite produced by Hypocrea sp. The structure of tanshisorbicin was determined using mass spectrometry, NMR spectroscopy, and ECD calculations. The anti-MRSA activity of 1 was found to be significantly higher than that of the parent substrate Tan IIA. Preliminary experiments indicate that tanshisorbicin is formed via a [4+2] cycloaddition reaction that is likely catalyzed by microbial enzyme.
Genome-guided investigation of anti-inflammatory sesterterpenoids with 5-15 trans-fused ring system from phytopathogenic fungi
Publisher: Springer Science and Business Media LLC
Date: 22-06-2021
Antitumor Activity and Cardiac Stimulatory Effects of Constituents of Anthopleura elegantissima
Publisher: Elsevier BV
Date: 11-1974
Abstract: TWEAK cytokine has been implicated in several biological responses including inflammation, angiogenesis, and osteoclastogenesis. We have investigated the role of TWEAK in regulating skeletal muscle mass. Addition of soluble TWEAK protein to cultured myotubes reduced the mean myotube diameter and enhanced the degradation of specific muscle proteins such as CK and MyHCf. The effect of TWEAK on degradation of MyHCf was stronger than its structural homologue, TNF-alpha. TWEAK increased the ubiquitination of MyHCf and the transcript levels of atrogin-1 and MuRF1 ubiquitin ligases. TWEAK inhibited phosphorylation of Akt kinase and its downstream targets GSK-3beta, FOXO1, mTOR, and p70S6K. Furthermore, TWEAK increased the activation of NF-kappaB transcription factor in myotubes. Adenoviral-mediated overexpression of IkappaB alpha deltaN (a degradation-resistant mutant of NF-kappaB inhibitory protein IkappaB alpha) in myotubes blocked the TWEAK-induced degradation of MyHCf. Chronic administration of TWEAK in mice resulted in reduced body and skeletal muscle weight with an associated increase in the activity of ubiquitin-proteasome system and NF-kappaB. Finally, muscle-specific transgenic overexpression of TWEAK decreased the body and skeletal muscle weight in mice. Collectively, our data suggest that TWEAK induces skeletal muscle atrophy through inhibition of the PI3K/Akt signaling pathway and activation of the ubiquitin-proteasome and NF-kappaB systems.
Plasmodium Gametocyte Inhibition Identified from a Natural-Product-Based Fragment Library
Publisher: American Chemical Society (ACS)
Date: 03-10-2013
DOI: 10.1021/CB400582B
Abstract: Fragment-based screening is commonly used to identify compounds with relatively weak but efficient localized binding to protein surfaces. We used mass spectrometry to study fragment-sized three-dimensional natural products. We identified seven securinine-related compounds binding to Plasmodium falciparum 2'-deoxyuridine 5'-triphosphate nucleotidohydrolase (PfdUTPase). Securinine bound allosterically to PfdUTPase, enhancing enzyme activity and inhibiting viability of both P. falciparum gametocyte (sexual) and blood (asexual) stage parasites. Our results provide a new insight into mechanisms that may be applicable to transmission-blocking agents.
Dysinosins B−D, Inhibitors of Factor VIIa and Thrombin from the Australian SpongeLamellodysideachlorea
Publisher: American Chemical Society (ACS)
Date: 09-07-2004
DOI: 10.1021/NP049968P
Abstract: Three new marine natural products, dysinosins B-D (1-3), were isolated from the sponge Lamellodysidea chlorea and their structures determined by 1D and 2D NMR spectroscopy. These compounds are inhibitors of the blood coagulation cascade serine proteases factor VIIa and thrombin. These analogues, dysinosins B-D (1-3), allowed identification of two structural motifs within the structures that contribute to binding to the proteases, factor VIIa and thrombin.
Myrtucommulones F−I, Phloroglucinols with Thyrotropin-Releasing Hormone Receptor-2 Binding Affinity from the Seeds of Corymbia scabrida
Publisher: American Chemical Society (ACS)
Date: 09-2008
DOI: 10.1021/NP800247U
Abstract: High-throughput screening of a plant and marine invertebrate extract library to find natural products with rat thyrotropin-releasing hormone (TRH) receptor-2 binding affinity led to the isolation of four new, myrtucommulones F-I (3-6), and two known, myrtucommulones A (1) and D (2), active acylphloroglucinols from the seeds of the Queensland tree Corymbia scabrida. Their structures were assigned from interpretation of 2D NMR and high-resolution ESIMS data. The relative configuration of the stereogenic centers for all six compounds was deduced from ROESY correlations. This is the first time that myrtucommulone A (1) has been isolated as a single pure compound. The structure of myrtucommulone D (2) has been revised. Myrtucommulones A, D, and F-I showed rat TRH receptor-2 binding affinity with IC50 values of 39, 11, 16, 24, 31, and 16 microM, respectively.
A Grand Challenge. 3. Unbiased Phenotypic Function of Metabolites from Australia Plants Gloriosa superba and Alangium villosum against Parkinson's Disease
Publisher: American Chemical Society (ACS)
Date: 06-05-2020
Study of the Novel Non-xanthine Heterocyclic Compound GU285 as a Potent Non-selective Adenosine Receptor Antagonist in the Rat
Publisher: Georg Thieme Verlag KG
Date: 26-12-2011
Abstract: The novel pyrazolo[3,4-d]pyrimidine compound GU285 (4-amino-6-alpha-carbamoylethylthio-1- phenylpyrazolo[3,4-d]pyrimidine, CAS 134896-40-5) was examined for its ability (1) to inhibit binding of adenosine (ADO) receptor ligands in rat brain membranes, (2) to antagonise functional responses to ADO agonists in rat right and left atria and coronary resistance vessels, and (3) to reduce the fall in heart rate and arterial blood pressure produced by the ADO A1 agonist N6-cyclopentyladenosine (CPA) in the intact, anaesthetized rat. GU285 competitively inhibited binding of the ADO A1 agonist [3H]-R-N6-phenylisopropyladenosine (R-PIA) yielding a Ki value of 11 (7-18) nmol.l-1 (geometric mean +/- 95% Cl). When assayed against the ADO A2A selective agonist [3H]-2-[p-(2-carboxyethyl)- phenethylamino]-5'-N-ethylcarboxamidoadenosine, (CGS21680), a Ki of 15 (10-24) nmol.l-1 was obtained. In spontaneously beating right atria, GU285 competitively antagonized negative chronotropic effects of R-PIA with a pA2 of 8.7 +/- 0.3 and in electrically paced left atria, GU285 competitively antagonized negative inotropic effects of R-PIA with a pA2 of 9.0 +/- 0.1. In the potassium-arrested, perfused rat heart GU285 (1 mumol.l-1) antagonized only the high sensitivity, ADO A2B mediated component of the biphasic relaxation of the coronary vasculature produced by NECA. The low sensitivity component was unchanged. GU285 (1 mumol.kg-1) antagonized the negative chronotropic and hypotensive effects of the adenosine A1 agonist CPA in anaesthetized rats, producing a 10-fold rightward shift in the dose-response relationship. These data demonstrate that in the rat, GU285 is a potent, non-selective adenosine receptor antagonist that maintains its activity in vivo.
4-(2-Thienyl)-1H-pyrrole-2-carbaldehyde
Publisher: International Union of Crystallography (IUCr)
Date: 24-09-2005
Design and synthesis of screening libraries based on the muurolane natural product scaffold
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2OB00029F
Abstract: The plant-derived natural product 14-hydroxy-6,12-muuroloadien-15-oic acid (1) was identified as a unique scaffold that could be chemically elaborated to generate novel lead- or drug-like screening libraries. Prior to synthesis a virtual library was generated and prioritised based on drug-like physicochemical parameters such as log P, log D(5.5), hydrogen bond donors/acceptors, and molecular weight. The natural product scaffold (1) was isolated from the endemic Australian plant Eremophila mitchellii and then utilised in the parallel solution-phase generation of two series of analogues. The first library consisted of six semi-synthetic amide derivatives, whilst the second contained six carbamate analogues. These libraries have been evaluated for antimalarial activity using a chloroquine-sensitive Plasmodium falciparum line (3D7) and several compounds displayed low to moderate activity with IC(50) values ranging from 14 to 33 μM.
Stimulating the proliferation, migration and lamellipodia of Schwann cells using low-dose curcumin.
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.NEUROSCIENCE.2016.02.073
Abstract: Transplantation of peripheral glia is being trialled for neural repair therapies, and identification of compounds that enhance the activity of glia is therefore of therapeutic interest. We have previously shown that curcumin potently stimulates the activity of olfactory glia. We have now examined the effect of curcumin on Schwann cell (SC) activities including proliferation, migration and the expression of protein markers. SCs were treated with control media and with different concentrations of curcumin (0.02-20 μM). Cell proliferation was determined by MTS assay and migration changes were determined by single live cell migration tracking. We found that small doses of curcumin (40 nM) dramatically increased the proliferation and migration in SCs within just one day. When compared with olfactory glia, curcumin stimulated SC proliferation more rapidly and at lower concentrations. Curcumin significantly increased the migration of SCs, and also increased the dynamic activity of lamellipodial waves which are essential for SC migration. Expression of the activated form of the MAP kinase p38 (p-p38) was significantly decreased in curcumin-treated SCs. These results show that curcumin's effects on SCs differ remarkably to its effects on olfactory glia, suggesting that subtypes of closely related glia can be differentially stimulated by curcumin. Overall these results demonstrate that the therapeutically beneficial activities of glia can be differentially enhanced by curcumin which could be used to improve outcomes of neural repair therapies.
4-AMINO-1-PHENYLPYRAZOLO[3,4-D]PYRIMIDIN-6(5H)-ONE, AN ISOGUANOSINE ANALOG
Publisher: CSIRO Publishing
Date: 1991
DOI: 10.1071/CH9911001
Abstract: 5-Amino-1-phenylpyrazole-4-carboxamide was condensed with benzoyl isothiocyanate. The resulting thiourea was treated with dicyclohexylcarbodiimide and annulated with ethanolic ammonia to yield 4-amino-1-phenylpyrazolo[3,4-d]pyrimidin-6(5H)-one. This product is a 1-phenylpyrazolo[3,4-d] pyrimidine analogue of the biologically active natural product, isoguanosine.
Aging Biology and Novel Targets for Drug Discovery
Publisher: Oxford University Press (OUP)
Date: 21-06-2012
Dereplication of cytotoxic compounds from different parts of Sophora pachycarpa using an integrated method of HPLC, LC-MS and 1H-NMR techniques
Publisher: Informa UK Limited
Date: 03-10-2016
DOI: 10.1080/14786419.2016.1239095
Abstract: Sophora pachycarpa Schrenk ex C.A.Mey. is an annual plant belonging to the family Fabaceae. The cytotoxic activities of methanol-dichloromethane extracts (1:1) of different parts of S. pachycarpa were investigated on DU145 (prostate cancer cell line) and MCF-7 (breast cancer cell line) cell lines. The root extract of S. pachycarpa was the only extract that showed significant cytotoxic activity with IC
New Galloylated Flavanonols from the Australian Plant Glochidion sumatranum
Publisher: Georg Thieme Verlag KG
Date: 07-2010
Abstract: Bioassay-guided fractionation of the CH(2)Cl(2)/MeOH extract from the Australian plant Glochidion sumatranum resulted in the isolation of four new galloylated flavanonols, (2R,3R)-dihydromyricetin-4'-O-(3''-O-methyl)-gallate (1), (2R,3R)-dihydromyricetin-3'-O-(3''-O-methyl)-gallate (2), (2R,3R)-dihydromyricetin-4'-O-gallate (3), and (2R,3R)-dihydromyricetin-3'-O-gallate (4), along with the known compound, (2R,3R)-dihydromyricetin (5). The structures of 1-5 were determined by NMR and MS analysis and their absolute configuration was elucidated by comparison of the CD data with literature values. Compounds 1/2 and 3/4 are two pairs of structural isomers that were shown to interconvert by transesterification during NMR and LC-MS studies. This process involved the intramolecular migration of the galloyl moieties between C-3' and C-4' of the flavanonol skeleton. Compounds 1 and 3 were identified as the more stable isomers. Compounds 1, 3, and 5 showed weak activity against the gram-negative bacterium Pseudomonas aeruginosa and the gram-positive bacterium Staphylococcus aureus.
Cytotoxic Evaluation of Alkaloids and Isoflavonoids from the Australian TreeErythrina vespertilio
Publisher: Georg Thieme Verlag KG
Date: 21-02-2012
Abstract: A new glucoalkaloid, vespertilioside, together with three known alkaloids, including 11- β-methoxyglucoerysovine, erysotrine, and hypaphorine, were isolated from the fruits of E. vespertilio Benth. In addition, three known isoflavonoids, including phaseollin, alpiniumisoflavone, and phaseollidin, were identified from the plant stems. The structures of compounds were determined by 1D/2D NMR and mass experiments. The cytotoxic activity of all compounds was evaluated against a metastatic prostate cancer cell line (PC3) and neonatal foreskin fibroblast (NFF) using a real-time label-free cell analyser. Among the tested compounds, phaseollidin showed cytotoxic activities against PC3 (IC (50) = 8.83 ± 1.87 µM) and NFF (0.64 ± 0.37 µM) cell lines.
Isolate from the Annelid, Reteterebella queenslandia (Australia), Active against Ehrlich Ascites Tumor
Publisher: Elsevier BV
Date: 09-1973
Abstract: Lower leg ischemia, myopathy, and limb dysfunction are distinguishing features of peripheral artery disease (PAD). The myopathy of PAD is characterized by myofiber degeneration in association with extracellular matrix expansion, and increased expression of transforming growth factor-beta 1 (TGF-β1 a pro-fibrotic cytokine). In this study, we evaluated cellular expression of TGF-β1 in gastrocnemius of control (CTRL) and PAD patients and its relationship to deposited collagen, fibroblast accumulation and limb hemodynamics. Gastrocnemius biopsies were collected from PAD patients with claudication (PAD-II N = 25) and tissue loss (PAD-IV N = 20) and from CTRL patients (N = 20). TGF-β1 in slide-mounted specimens was labeled with fluorescent antibodies and analyzed by quantitative wide-field, fluorescence microscopy. We evaluated co-localization of TGF-β1 with vascular smooth muscle cells (SMC) (high molecular weight caldesmon), fibroblasts (TE-7 antigen), macrophages (CD163), T cells (CD3) and endothelial cells (CD31). Collagen was stained with Masson Trichrome and collagen density was determined by quantitative bright-field microscopy with multi-spectral imaging. Collagen density increased from CTRL to PAD-II to PAD-IV specimens (all differences p < 0.05) and was prominent around microvessels. TGF-β1 expression increased with advancing disease (all differences p < 0.05), correlated with collagen density across all specimens (r = 0.864 p < 0.001), associated with fibroblast accumulation, and was observed exclusively in SMC. TGF-β1 expression inversely correlated with ankle-brachial index across PAD patients (r = -0.698 p < 0.001). Our findings support a progressive fibrosis in the gastrocnemius of PAD patients that is caused by elevated TGF-β1 production in the SMC of microvessels in response to tissue hypoxia.
Dereplication of antioxidant compounds in Bene ( Pistacia atlantica subsp. mutica ) hull using a multiplex approach of HPLC–DAD, LC–MS and 1 H NMR techniques
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.JPBA.2015.09.005
Abstract: Bene is an edible fruit from the tree Pistacia atlantica subsp. mutica, and is of steadily growing interest in recent years due to its significant antioxidant properties and potential health benefits. An antioxidant activity-guided fractionation of the methanol extract from Bene hull together with an integrated approach of HPLC-DAD, LC-MS and (1)H NMR techniques led to the identification of main antioxidant phenolic compounds for the first time. Radical scavenging activity of each fraction/compound was tested using DPPH and FRAP assays. The phenolic content of the fractions was also determined by Folin-Ciocalteu's method. The main identified antioxidant compounds were luteolin (46.53% w/w of total extract), gallic acid (9.84% w/w), 2″-O-galloylisoquercitrin (0.53% w/w), quercetin 3-rutinoside (0.34% w/w) and 2″-O-cis-caffeoylquercitrin (0.26% w/w). The minor antioxidant compounds were also identified by liquid chromatography-positive/negative electrospray ionization tandem mass spectrometry. The structure-antioxidant activity relationship of identified phenolics are also discussed in this paper.
4-Iodo-1H-pyrrole-2-carbaldehyde
Publisher: International Union of Crystallography (IUCr)
Date: 21-09-2007
Quaternized Acridine Maleimide MALDI Probe Enables Mass Spectrometry Imaging of Thiols
Publisher: American Chemical Society (ACS)
Date: 21-10-2022
DOI: 10.1021/ACS.ANALCHEM.2C02292
Abstract: Thiols are essential metabolites associated with redox imbalances and metabolic disorders in diseases. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) facilitates imaging of metabolites in tissue, but imaging of thiols remains challenging. Here we developed a method to visualize thiols using a stable isotope-labeled (SIL) MALDI probe, a mixture of unlabeled and deuterium-labeled reagents that provided adduct signals at [M]
Drug-Repurposing Screening Identifies a Gallic Acid Binding Site on SARS-CoV-2 Non-structural Protein 7
Publisher: American Chemical Society (ACS)
Date: 07-03-2023
Exiguaquinol: A Novel Pentacyclic Hydroquinone from Neopetrosia exigua that Inhibits Helicobacter pylori MurI
Publisher: American Chemical Society (ACS)
Date: 20-05-2008
DOI: 10.1021/OL800898Z
Abstract: Bioassay-guided fractionation of the methanol extract of the Australian sponge Neopetrosia exigua led to the isolation of exiguaquinol (2), a new pentacyclic hydroquinone that inhibited Helicobacter pylori glutamate racemase (MurI) with an IC(50) of 4.4 microM. Its structure and relative configuration were assigned on the basis of spectroscopic data. Exiguaquinol (2), bearing a novel pentacyclic ring skeleton, is the first natural product to show inhibition of H. pylori MurI. Its protein-ligand modeling is also discussed.
Front-Loading Natural-Product-Screening Libraries for logP:Background, Development, and Implementation
Publisher: Wiley
Date: 04-2013
Abstract: In the period from January 1981 to December 2010, 1068 small-molecule new chemical entities (NCEs) were introduced, of which ca. 34% are either a natural product or a close analogue. While this metric reflects the impact natural products have played in delivering new chemical starting points (leads) for the pharmaceutical industry, it does not capture the decline this approach has suffered over the last 20 years as the high-throughput screening (HTS) of pure compound libraries has become more popular. An impediment to natural-product drug discovery in the HTS paradigm is the lack of a clear strategy that enables front-loading of an extract or fraction's chemical constituents so that they are compliant with lead- and drug-like chemical space. To address this imbalance, an approach based on lipophilicity, as measured by clog P has been developed that, together with advances being made in isolation and structural elucidation, can afford natural product leads in timelines compatible with pure compound screening.
Design and Synthesis of Natural Product Inspired Libraries Based on the Three-Dimensional (3D) Cedrane Scaffold: Toward the Exploration of 3D Biological Space
Publisher: American Chemical Society (ACS)
Date: 13-07-2018
DOI: 10.1021/ACS.JMEDCHEM.8B00194
Abstract: A chemoinformatic method was developed to extract nonflat scaffolds embedded in natural products within the Dictionary of Natural Products (DNP). The cedrane scaffold was then chosen as an ex le of a nonflat scaffold that directs substituents in three-dimensional (3D) space. A cedrane scaffold that has three orthogonal handles to allow generation of 1D, 2D, and 3D libraries was synthesized on a large scale. These libraries would cover more than 50% of the natural ersity of natural products with an embedded cedrane scaffold. Synthesis of three focused natural product-like libraries based on the 3D cedrane scaffold was achieved. A phenotypic assay was used to test the biological profile of synthesized compounds against normal and Parkinson's patient-derived cells. The cytological profiles of the synthesized analogues based on the cedrane scaffold revealed that this 3D scaffold, prevalidated by nature, can interact with biological systems as it displayed various effects against normal and Parkinson's patient-derived cell lines.
L-Azetidine-2-carboxylic acid, the antidermatophyte constituent of two marine sponges
Publisher: Springer Science and Business Media LLC
Date: 06-1978
DOI: 10.1007/BF01947258
Carbene induced rearrangement products from two furoquinolinone scaffolds
Publisher: Wiley
Date: 07-2010
DOI: 10.1002/JHET.463
Hasubanan Alkaloids with δ-Opioid Binding Affinity from the Aerial Parts of Stephania japonica
Publisher: American Chemical Society (ACS)
Date: 28-04-2010
DOI: 10.1021/NP100009J
Abstract: Two new (1 and 2) and six known hasubanan alkaloids (3-8) and one morphinane alkaloid (9) were isolated from the leaves of the North Queensland rainforest vine Stephania japonica. The structures of 1 and 2 were determined by interpretation of their 1D and 2D NMR spectra. The hasubanan alkaloids showed affinity for the human delta-opioid receptor with IC(50) values ranging from 0.7 to 46 microM. The compounds were also tested for their affinity to micro- and kappa-opioid receptors and shown to be inactive against kappa-opioid receptors, but were of similar potency against the micro-opioid receptor.
Sexual and Apomictic Seed Formation in Hieracium Requires the Plant Polycomb-Group Gene FERTILIZATION INDEPENDENT ENDOSPERM
Publisher: Oxford University Press (OUP)
Date: 09-2008
Abstract: A Polycomb-Group (PcG) complex, FERTILIZATION INDEPENDENT SEED (FIS), represses endosperm development in Arabidopsis thaliana until fertilization occurs. The Hieracium genus contains apomictic species that form viable seeds asexually. To investigate FIS function during apomictic seed formation, FERTILIZATION INDEPENDENT ENDOSPERM (FIE), encoding a WD-repeat member of the FIS complex, was isolated and downregulated in sexual and apomictic Hieracium species. General downregulation led to defects in leaf and seed development, consistent with a role in developmental transitions and cell fate. PcG-like activity of Hieracium FIE was also supported by its interaction in vitro with the Arabidopsis CURLY LEAF PcG protein. By contrast, specific downregulation of FIE in developing seeds of sexual Hieracium did not result in autonomous endosperm proliferation but led to seed abortion after cross-pollination. Furthermore, in apomictic Hieracium, specific FIE downregulation inhibited autonomous embryo and endosperm initiation, and most autonomous seeds displayed defective embryo and endosperm growth. Therefore, FIE is required for both apomictic and fertilization-induced seed initiation in Hieracium. Since Hieracium FIE failed to interact with FIS class proteins in vitro, its partner proteins might differ from those in the FIS complex of Arabidopsis. These differences in protein interaction were attributed to structural modifications predicted from comparisons of Arabidopsis and Hieracium FIE molecular models.
Pyrazolo[3,4-d]pyrimidines: C4, C6 substitution leads to adenosine A1 receptor selectivity
Publisher: Elsevier BV
Date: 02-1996
ApoE secretion modulating bromotyrosine derivative from the Australian marine sponge Callyspongia sp.
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.BMCL.2014.05.054
Abstract: High throughput screening of a pre-fractionated natural product library identified 11 active fractions showing ApoE modulation activity. Mass-directed fractionation of one active crude extract from the Australian marine sponge Callyspongia sp. resulted in the isolation of 13 metabolites, including three new bromotyrosine derivatives, callyspongic acid (1), 3,5-dibromo-4-methoxyphenylpyruvic acid (2), N-acetyl-3-bromo-4-hydroxylphenylethamine (3), and ten known compounds (4-13). The structure elucidation of compounds 1-3 was based on their 1D and 2D NMR and MS spectroscopic data. 3,5-Dibromo-4-methoxyphenylpyruvic acid (2) showed weak activity in increasing the apolipoprotein E secretion from human CCF-STTG1 cells at the concentration of 40 μM.
Natural products as lead structures: chemical transformations to create lead-like libraries
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.DRUDIS.2013.10.013
Abstract: In this review, we analyze and illustrate the variation of the two main lead-like descriptors [molecular weight (MW) and the partition coefficient (logP)] in the generation of libraries in which a natural product (NP) is used as the guiding structure. Despite the different approaches used to create NP-like libraries, controlling these descriptors during the synthetic process is important to generate lead-like libraries. From this analysis, we present a schematic approach to the generation of lead-like libraries that can be applied to any starting NP.
The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C7NP00064B
Abstract: With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets.
N1,N1-Dimethyl-N3-(3-(trifluoromethyl)phenethyl)propane-1,3-diamine, a new lead for the treatment of human African trypanosomiasis
Publisher: Elsevier BV
Date: 03-2014
Maculotoxin: A Neurotoxin from the Venom Glands of the Octopus Hapalochlaena maculosa Identified as Tetrodotoxin
Publisher: American Association for the Advancement of Science (AAAS)
Date: 13-01-1978
Abstract: Maculotoxin, a potent neurotoxin isolated from the posterior salivary glands of the blue-ringed octopus. Hapalochlaena maculosa, has now been identified as tetrodotoxin. This is the first reported case in which tetrodotoxin has been found to occur in a venom.
Monoterpene Glycoside ESK246 from Pittosporum Targets LAT3 Amino Acid Transport and Prostate Cancer Cell Growth
Publisher: American Chemical Society (ACS)
Date: 05-05-2014
DOI: 10.1021/CB500120X
The Synthesis of Two Combinatorial Libraries Using a 4-(2-Thienyl)-pyrrole Template
Publisher: CSIRO Publishing
Date: 2002
DOI: 10.1071/CH02110
Abstract: The synthesis of the novel biaryl compound, 4-(2-thienyl)-1H-pyrrole-2-carbaldehyde (1), by Suzuki–Miyaura coupling conditions is reported. Compound (1) was subsequently used as a combinatorial template in the parallel solution-phase synthesis of an amine and imine compound library. The amine library was produced using reductive amination conditions, and purification was achieved by a liquid–liquid partition followed by silica chromatography to afford ten amine analogues. The imine library consisted of five compounds, which were synthesized using volatile primary amines that allowed purification by evaporation. The synthesis of the novel and related biaryl carbaldehyde, tert-butyl-2-(5-formyl-1H-pyrrol-3-yl)-1H-pyrrole-1-carboxylate (2) is also reported.
Pim2 Inhibitors from the Papua New Guinean Plant Cupaniopsis macropetala
Publisher: American Chemical Society (ACS)
Date: 25-10-0012
DOI: 10.1021/NP070431W
Abstract: Bioassay-guided fractionation of an organic extract from the leaves of Cupaniopsis macropetala resulted in the isolation of a new alkaloid, galloyl tyramine ( 1), together with the known flavonoid glycoside quercitrin ( 2). The structure of 1 was determined following 1D and 2D NMR, IR, UV, and MS data analysis. Compounds 1 and 2 displayed IC 50 values of 161 and 25 microM, respectively, in a Pim2 enzyme assay.
Aplysamine 6, an Alkaloidal Inhibitor of Isoprenylcysteine Carboxyl Methyltransferase from the Sponge Pseudoceratina sp.
Publisher: American Chemical Society (ACS)
Date: 05-04-2008
DOI: 10.1021/NP0706623
Abstract: The anticancer target isoprenylcysteine carboxyl methyltransferase (Icmt) was the focus of a natural product high-throughput screening c aign. The Australian marine sponge Pseudoceratina sp. yielded aplysamine 6, a new bromotyrosine derivative with an alpha,beta-unsaturated amide linkage, as the bioactive constituent. Its structure was determined by 1D and 2D NMR spectroscopy.
Convolutamines I and J, antitrypanosomal alkaloids from the bryozoan Amathia tortusa
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.BMC.2011.06.006
Abstract: Mass-directed isolation of the CH(2)Cl(2)/CH(3)OH extract from the marine bryozoan Amathia tortusa resulted in the purification of two new brominated alkaloids, convolutamines I (1) and J (2). The structures of 1 and 2 were determined following spectroscopic data analysis. Both compounds were isolated during a drug discovery program aimed at identifying new antitrypanosomal leads from a prefractionated natural product library. Compounds 1 and 2 were shown to be active toward the parasite Trypanosoma brucei brucei with IC(50) values of 1.1 and 13.7 μM, respectively. Preliminary toxicity profiling was also performed on both 1 and 2 using the human embryonic kidney cell line, HEK293. Compound 1 was shown to exhibit cytotoxicity against HEK293 with an IC(50) of 22.0 μM whilst 2 was inactive at 41.0 μM.
Achyrodimer F, a tyrosyl-DNA phosphodiesterase I inhibitor from an Australian fungus of the family Cortinariaceae
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.BMCL.2017.07.062
Abstract: Mass-guided isolation of the dichloromethane/methanol extracts from a specimen of teleomorphic fungus of the family Cortinariaceae resulted in the identification of a new dimeric cyclobutane metabolite, achyrodimer F (1), along with the monomers hispidin (2) and bisnoryangonin (3). Their structures were determined by NMR and MS data analyses. Density Function Theory (DFT) NMR calculations was employed to confirm the chemical structure of achyrodimer F. Compound 1 inhibited tyrosyl-DNA phosphodiesterase I with an IC
Discovery of a Natural Product That Binds to the Mycobacterium tuberculosis Protein Rv1466 Using Native Mass Spectrometry
Publisher: MDPI AG
Date: 21-05-2020
DOI: 10.3390/MOLECULES25102384
Abstract: Elucidation of the mechanism of action of compounds with cellular bioactivity is important for progressing compounds into future drug development. In recent years, phenotype-based drug discovery has become the dominant approach to drug discovery over target-based drug discovery, which relies on the knowledge of a specific drug target of a disease. Still, when targeting an infectious disease via a high throughput phenotypic assay it is highly advantageous to identifying the compound’s cellular activity. A fraction derived from the plant Polyalthia sp. showed activity against Mycobacterium tuberculosis at 62.5 μge/μL. A known compound, altholactone, was identified from this fraction that showed activity towards M. tuberculosis at an minimum inhibitory concentration (MIC) of 64 μM. Retrospective analysis of a target-based screen against a TB proteome panel using native mass spectrometry established that the active fraction was bound to the mycobacterial protein Rv1466 with an estimated pseudo-Kd of 42.0 ± 6.1 µM. Our findings established Rv1466 as the potential molecular target of altholactone, which is responsible for the observed in vivo toxicity towards M. tuberculosis.
Peculiarities of meroterpenoids and their bioproduction
Publisher: Springer Science and Business Media LLC
Date: 05-2021
Identifying New Ligands for JNK3 by Fluorescence Thermal Shift Assays and Native Mass Spectrometry
Publisher: American Chemical Society (ACS)
Date: 14-04-2022
Synthesis of cyclic peptides modelled on the microcystin and nodularin rings
Publisher: Elsevier BV
Date: 09-1996
Antimicrobial Benzyltetrahydroisoquinoline-Derived Alkaloids from the Leaves of Doryphora aromatica
Publisher: American Chemical Society (ACS)
Date: 05-03-2021
Cheilanthane sesterterpenes, protein kinase inhibitors, from a marine sponge of the genus Ircinia
Publisher: American Chemical Society (ACS)
Date: 13-02-2001
DOI: 10.1021/NP0004597
Abstract: Four cheilanthane sesterterpenoids, 25-hydroxy-13(24),15,17-cheilanthatrien-19,25-olide (1), 13,16-epoxy-25-hydroxy-17-cheilanthen-19,25-olide (2), 25-hydroxy-13(24),17-cheilanthadien-16,19-olide (3), and 16,25-dihydroxy-13(24),17-cheilanthadien-19,25-olide (4), were isolated from the marine sponge Irciniasp. Compounds 1, 3, and 4 are new natural products. The four compounds inhibit MSK1 (mitogen and stress activated kinase) and MAPKAPK-2 (mitogen activated protein kinase activated protein kinase), two protein kinases involved in mitogen and stress signal transduction.
Axinellamines A−D, Novel Imidazo−Azolo−Imidazole Alkaloids from the Australian Marine Sponge Axinella sp.
Publisher: American Chemical Society (ACS)
Date: 14-01-1999
DOI: 10.1021/JO981034G
Abstract: Four imidazo-azolo-imidazole alkaloids, axinellamines A-D, have been isolated from an Australian marine sponge, Axinella sp. (order: Halichondrida: family: Axinellidae). These compounds contain a unique perhydrocyclopenta-imidazo-azolo-imidazole carbon skeleton. Three of these compounds had bactericidal activity against Helicobacter pylori at 1000 &mgr M.
Ianthelliformisamines A-C, Antibacterial Bromotyrosine-Derived Metabolites from the Marine Sponge Suberea ianthelliformis
Publisher: American Chemical Society (ACS)
Date: 19-04-2012
DOI: 10.1021/NP300147D
Abstract: A high-throughput screening c aign using a prefractionated natural product library and an in vitro Pseudomonas aeruginosa (PAO200 strain) assay identified two antibacterial fractions derived from the marine sponge Suberea ianthelliformis. Mass-directed isolation of the CH(2)Cl(2)/CH(3)OH extract from S. ianthelliformis resulted in the purification of three new bromotyrosine-derived metabolites, ianthelliformisamines A-C (1-3), together with the known natural products aplysamine 1 (4) and araplysillin I (5). The structures of 1-3 were determined following analysis of 1D and 2D NMR and MS spectroscopic data. This is the first report of chemistry from the marine sponge S. ianthelliformis. Ianthelliformisamine A (1) showed inhibitory activity against the Gram-negative bacterium P. aeruginosa with an IC(50) value of 6.8 μM (MIC = 35 μM).
Dragmacidol A and dragmacidolide A from the Australian marine sponge Dragmacidon australe
Publisher: Elsevier BV
Date: 09-2015
Bromotyrosine Alkaloids from the Australian Marine Sponge Pseudoceratina verrucosa
Publisher: American Chemical Society (ACS)
Date: 14-03-2013
DOI: 10.1021/NP300648D
Abstract: Two new bromotyrosine alkaloids, pseudoceralidinone A (1) and aplysamine 7 (2), along with three known compounds were isolated from the Australian sponge Pseudoceratina verrucosa. Their structures were characterized by NMR and MS data and the synthetic route. Their cytotoxicity was evaluated against cancer cell lines (HeLa and PC3) and a noncancer cell line (NFF).
Euodenine A: A Small-Molecule Agonist of Human TLR4
Publisher: American Chemical Society (ACS)
Date: 07-02-2014
DOI: 10.1021/JM401321V
Abstract: A small-molecule natural product, euodenine A (1), was identified as an agonist of the human TLR4 receptor. Euodenine A was isolated from the leaves of Euodia asteridula (Rutaceae) found in Papua New Guinea and has an unusual U-shaped structure. It was synthesized along with a series of analogues that exhibit potent and selective agonism of the TLR4 receptor. SAR development around the cyclobutane ring resulted in a 10-fold increase in potency. The natural product demonstrated an extracellular site of action, which requires the extracellular domain of TLR4 to stimulate a NF-κB reporter response. 1 is a human-selective agonist that is CD14-independent, and it requires both TLR4 and MD-2 for full efficacy. Testing for immunomodulation in PBMC cells shows the induction of the cytokines IL-8, IL-10, TNF-α, and IL-12p40 as well as suppression of IL-5 from activated PBMCs, indicating that compounds like 1 could modulate the Th2 immune response without causing lung damage.
Small-molecule inhibitors of the cancer target, isoprenylcysteine carboxyl methyltransferase, from Hovea parvicalyx
Publisher: Elsevier BV
Date: 06-2008
DOI: 10.1016/J.PHYTOCHEM.2008.04.011
Abstract: Isoprenylcysteine carboxyl methyltransferase (Icmt) is enzyme target in anticancer drug discovery. An Icmt natural product high-throughput screening c aign was conducted and a hit extract from the roots of Hovea parvicalyx was identified. 2'-Methoxy-3'-prenyl-licodione and 2'-methoxy-3',3''-diprenyl-licodione, two prenylated beta-hydroxychalcone compounds, together with the known flavanone (S)-glabrol, were isolated and identified as bioactive constituents. Their structures were determined largely by 1D and 2D NMR spectroscopy.
Determination of Analyte Concentration Using the Residual Solvent Resonance in 1H NMR Spectroscopy
Publisher: American Chemical Society (ACS)
Date: 05-04-2008
DOI: 10.1021/NP8000046
Abstract: An NMR protocol that uses the residual proton signal from DMSO -d(6) (i.e., DMSO -d(5)) to determine the concentration of an analyte in a NMR s le was developed. This technique provides an alternative method for determining the molar concentration of compounds in solution without prior knowledge of their molecular weight. The method is particularly useful when submilligram quantities of compound are to be analyzed and is applicable to a variety of different research areas such as compound management, and natural product, combinatorial, and medicinal chemistry.
Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry
Publisher: American Chemical Society (ACS)
Date: 13-02-0001
ent-Labdane Diterpenes from the Stems of Mallotus japonicus
Publisher: American Chemical Society (ACS)
Date: 30-08-2013
DOI: 10.1021/NP400241P
Abstract: Eight new ent-labdane diterpenoids, mallonicusins A-H (1-8), were isolated from the stems of Mallotus japonicus. Their structures, including the absolute configurations, were determined by extensive analyses of spectroscopic data and the ECD spectra of the Pr(FOD)₃ complex of substrates in CCl₄. The absolute configuration of compound 1 was confirmed by single-crystal X-ray crystallography using Cu Kα radiation.
Antimalarial Benzylisoquinoline Alkaloid from the Rainforest Tree Doryphora sassafras
Publisher: American Chemical Society (ACS)
Date: 28-07-2009
DOI: 10.1021/NP9002564
Abstract: Mass-directed isolation of the CH(2)Cl(2)/MeOH extract of Doryphora sassafras resulted in the purification of a new benzylisoquinoline alkaloid, 1-(4-hydroxybenzyl)-6,7-methylenedioxy-2-methylisoquinolinium trifluoroacetate (1), and the known aporphine alkaloid (S)-isocorydine (2). The structures of 1 and 2 were determined by 1D and 2D NMR and MS data analyses. The compounds were isolated during a drug discovery program aimed at identifying new antimalarial leads from a prefractionated natural product library. When tested against two different strains of the parasite Plasmodium falciparum (3D7 and Dd2), 1 displayed IC(50) values of 3.0 and 4.4 microM, respectively. Compound 1 was tested for cytotoxicity toward a human embryonic kidney cell line (HEK293) and displayed no activity at 120 microM.
Identifying common metalloprotease inhibitors by protein fold types using Fourier Transform Mass Spectrometry
Publisher: Elsevier BV
Date: 12-2007
DOI: 10.1016/J.BMCL.2007.09.084
Abstract: Fourteen natural products, known to inhibit other proteins of the Zincin-like fold class, were screened for inhibition of the Zincin-like fold metalloprotease thermolysin using mass spectrometry. Fourier Transform Mass Spectrometry was successful in identifying actinonin, a known inhibitor of astacin and stromelysin, to be an inhibitor of thermolysin. Molecular modelling studies have shown that specificity within the Zincin-like fold is determined by Protein Fold Topology.
The re-emergence of natural products for drug discovery in the genomics era
Publisher: Springer Science and Business Media LLC
Date: 23-01-2015
DOI: 10.1038/NRD4510
Abstract: Natural products have been a rich source of compounds for drug discovery. However, their use has diminished in the past two decades, in part because of technical barriers to screening natural products in high-throughput assays against molecular targets. Here, we review strategies for natural product screening that harness the recent technical advances that have reduced these barriers. We also assess the use of genomic and metabolomic approaches to augment traditional methods of studying natural products, and highlight recent ex les of natural products in antimicrobial drug discovery and as inhibitors of protein-protein interactions. The growing appreciation of functional assays and phenotypic screens may further contribute to a revival of interest in natural products for drug discovery.
Chemoinformatic Analysis as a Tool for Prioritization of Trypanocidal Marine Derived Lead Compounds
Publisher: MDPI AG
Date: 04-03-2014
DOI: 10.3390/MD12031169
Ianthesine E, a new bromotyrosine-derived metabolite from the Great Barrier Reef sponge Pseudoceratina sp.
Publisher: Informa UK Limited
Date: 20-09-2008
DOI: 10.1080/14786410701763411
Abstract: The new compound ianthesine E (1) was isolated from the Great Barrier Reef marine sponge Pseudoceratina sp. along with the known metabolites 11-hydroxyaerothionin (2), aerothionin (3) and 11,19-dideoxyfistularin 3 (4). Structures were determined on the basis of their spectroscopic data. The compounds were tested for inhibition of [(3)H] DPCPX binding to adenosine A(1) receptors in a whole cell binding assay. At 100 microM, aerothionin was the most potent, inhibiting 67% of binding, followed by ianthesine E and 11-hydroxyaerothionin which inhibited 61% of binding, and 11,19-dideoxyfistularin which initiated 51% of binding Ianthesine E (EC(50) 60 microM), aerothionin (EC(50) 42 microM) and 11,19-dideoxyfistularin-3 (EC(50) 2.6 microM) exhibited moderate cytotoxicity against the HeLa cell line.
Stimulation of guinea-pig brain adenylate cyclase by adenosine analogues with potent pharmacological activity
Publisher: Elsevier BV
Date: 03-1980
DOI: 10.1016/0024-3205(80)90254-4
Abstract: The objective of this study was to determine if absent air conduction stimuli vestibular evoked myogenic potential (VEMP) responses found in ears after cochlear implantation can be the result of alterations in peripheral auditory mechanics rather than vestibular loss. Peripheral mechanical changes were investigated by comparing the response rates of air and bone conduction VEMPs as well as by measuring and evaluating wideband acoustic immittance (WAI) responses in ears with cochlear implants and normal-hearing control ears. The hypothesis was that the presence of a cochlear implant can lead to an air-bone gap, causing absent air conduction stimuli VEMP responses, but present bone conduction vibration VEMP responses (indicating normal vestibular function), with changes in WAI as compared with ears with normal hearing. Further hypotheses were that subsets of ears with cochlear implants would (a) have present VEMP responses to both stimuli, indicating normal vestibular function and either normal or near-normal WAI, or (b) have absent VEMP responses to both stimuli, regardless of WAI, due to true vestibular loss. Twenty-seven ears with cochlear implants (age range 7 to 31) and 10 ears with normal hearing (age range 7 to 31) were included in the study. All ears completed otoscopy, audiometric testing, 226 Hz tympanometry, WAI measures (absorbance), air conduction stimuli cervical and ocular VEMP testing through insert earphones, and bone conduction vibration cervical and ocular VEMP testing with a mini-shaker. Comparisons of VEMP responses to air and bone conduction stimuli, as well as absorbance responses between ears with normal hearing and ears with cochlear implants, were completed. All ears with normal hearing demonstrated 100% present VEMP response rates for both stimuli. Ears with cochlear implants had higher response rates to bone conduction vibration compared with air conduction stimuli for both cervical and ocular VEMPs however, this was only significant for ocular VEMPs. Ears with cochlear implants demonstrated reduced low-frequency absorbance (500 to 1200 Hz) as compared with ears with normal hearing. To further analyze absorbance, ears with cochlear implants were placed into subgroups based on their cervical and ocular VEMP response patterns. These groups were (1) present air conduction stimuli response, present bone conduction vibration response, (2) absent air conduction stimuli response, present bone conduction vibration response, and (3) absent air conduction stimuli response, absent bone conduction vibration response. For both cervical and ocular VEMPs, the group with absent air conduction stimuli responses and present bone conduction vibration responses demonstrated the largest decrease in low-frequency absorbance as compared with the ears with normal hearing. Bone conduction VEMP response rates were increased compared with air-conduction VEMP response rates in ears with cochlear implants. Ears with cochlear implants also demonstrate changes in low-frequency absorbance consistent with a stiffer system. This effect was largest for ears that had absent air conduction but present bone conduction VEMPs. These findings suggest that this group, in particular, has a mechanical change that could lead to an air-bone gap, thus, abolishing the air conduction VEMP response due to an alteration in mechanics and not a true vestibular loss. Clinical considerations include using bone conduction vibration VEMPs and WAI for preoperative and postoperative testing in patients undergoing cochlear implantation.
Optimization of Electrospray Ionization by Statistical Design of Experiments and Response Surface Methodology: Protein–Ligand Equilibrium Dissociation Constant Determinations
Publisher: American Chemical Society (ACS)
Date: 25-05-2016
Marine natural products from sponges (Porifera) of the order Dictyoceratida (2013 to 2019); a promising source for drug discovery
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0RA04408C
Abstract: Marine organisms have been considered an interesting target for the discovery of different classes of secondary natural products with wide-ranging biological activities.
Collision-Induced Affinity Selection Mass Spectrometry for Identification of Ligands
Publisher: American Chemical Society (ACS)
Date: 18-05-2022
Advantages of Molecular Weight Identification during Native MS Screening
Publisher: Georg Thieme Verlag KG
Date: 09-05-2018
DOI: 10.1055/A-0608-4870
Abstract: Native mass spectrometry detection of ligand-protein complexes allowed rapid detection of natural product binders of apo and calcium-bound S100A4 (a member of the metal binding protein S100 family), T cell/transmembrane, immunoglobulin (Ig), and mucin protein 3, and T cell immunoreceptor with Ig and ITIM (immunoreceptor tyrosine-based inhibitory motif) domains precursor protein from extracts and fractions. Based on molecular weight common hits were detected binding to all four proteins. Seven common hits were identified as apigenin 6-C-β-D-glucoside 8-C-α-L-arabinoside, sweroside, 4′,5-dihydroxy-7-methoxyflavanone-6-C-rutinoside, loganin acid, 6-C-glucosylnaringenin, biochanin A 7-O-rutinoside and quercetin 3-O-rutinoside. Mass guided isolation and NMR identification of hits confirmed the mass accuracy of the ligand in the ligand-protein MS complexes. Thus, molecular weight ID from ligand-protein complexes by electrospray ionization Fourier transform mass spectrometry allowed rapid dereplication. Native mass spectrometry using electrospray ionization Fourier transform mass spectrometry is a tool for dereplication and metabolomics analysis.
Sideroxylonal C, a New Inhibitor of Human Plasminogen Activator Inhibitor Type-1, from the Flowers of Eucalyptus albens
Publisher: American Chemical Society (ACS)
Date: 23-01-1999
DOI: 10.1021/NP980286+
Dictamins A-C, three unprecedented apotirucallane-type trinortriterpenoids from Dictamnus dasycarpus
Publisher: Elsevier BV
Date: 08-2013
Calcium channels and iron metabolism: A redox catastrophe in Parkinson's disease and an innovative path to novel therapies?
Publisher: Elsevier BV
Date: 11-2021
A brominated bisacetylenic acid from the marine sponge
Publisher: Elsevier BV
Date: 1985
Progress toward establishing an open access molecular screening capability in the Australasian region
Publisher: American Chemical Society (ACS)
Date: 12-2007
DOI: 10.1021/CB7002384
Dysinosin A: A Novel Inhibitor of Factor VIIa and Thrombin from a New Genus and Species of Australian Sponge of the Family Dysideidae
Publisher: American Chemical Society (ACS)
Date: 17-10-2002
DOI: 10.1021/JA020814A
Abstract: A new marine natural product dysinosin A 1 has been isolated from a new genus and species of sponge of the family Dysideidae found near Lizard Island, North Queensland, Australia. Dysinosin A is a potent inhibitor of the blood coagulation cascade factor VIIa and an inhibitor of the serine protease thrombin. Among the distinctive features of dysinosin A are the presence of a 5,6-dihydroxy-octahydroindole-2-carboxylic acid, 3-amino-ethyl 1-N-amidino-Delta-3-pyrroline, a sulfated glyceric acid, and d-leucine, assembled through three peptidic linkages. Dysinosin A inhibited factor VIIa at a Ki of 108 nM and thrombin at a Ki of 452 nM. The identification of the 1-N-amidino-Delta-3-pyrroline and 5,6-dihydroxy-octahydroindole-2-carboxylic acid as P1 and P2 moieties respectively, should pave the way for the design and synthesis of new structure-based inhibitors.
Is it time for artificial intelligence to predict the function of natural products based on 2D-structure
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9MD00128J
Abstract: One of chemistry's grand challenges is to find a function for every known metabolite. We explore the opportunity for artificial intelligence to provide rationale interrogation of metabolites to predict their function.
A robust clustering approach for NMR spectra of natural product extracts
Publisher: Wiley
Date: 2005
DOI: 10.1002/MRC.1562
Abstract: A robust method was developed to cluster similar NMR spectra from partially purified extracts obtained from a range of marine sponges and a plant biota. The NMR data were acquired using microtiter plate NMR (VAST) in protonated solvents. A s le data set which contained several clusters was used to optimize the protocol. The evaluation of the robustness was performed using three different clustering methods: tree clustering analysis, K-means clustering and multidimensional scaling. These methods were compared for consistency using the s le data set and the optimized methodology was applied to clustering of a set of spectra from partially purified biota extracts.
1,2-Bis(1H-indol-3-yl)ethane-1,2-dione, an Indole Alkaloid from the Marine Sponge Smenospongia sp.
Publisher: American Chemical Society (ACS)
Date: 13-03-2002
DOI: 10.1021/NP010347V
Abstract: 1,2-Bis(1H-indol-3-yl)ethane-1,2-dione (1), a bisindole alkaloid, was isolated from the marine sponge Smenospongia sp. The known compounds indole-3-carbaldehyde (2), 6-bromoindole-3-carbaldehyde (3), and tryptamine (4) and mixtures of the (Z/E) isomers of 6-bromo-2'-demethylaplysinopsin (5a/5b) and 6-bromo-3'-deimino-2',4'-bis(demethyl)-3'-oxoaplysinopsin (6a/6b) were also isolated.
Two new antioxidant actinosporin analogues from the calcium alginate beads culture of sponge-associated Actinokineospora sp. strain EG49
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.BMCL.2014.08.068
Abstract: Marine sponge-associated actinomycetes represent an exciting new resource for the identification of new and novel natural products . Previously, we have reported the isolation and structural elucidation of actinosporins A (1) and B (2) from Actinokineospora sp. strain EG49 isolated from the marine sponge Spheciospongia vagabunda. Herein, by employing different fermentation conditions on the same microorganism, we report on the isolation and antioxidant activity of structurally related metabolites, actinosporins C (3) and D (4). The antioxidant potential of actinosporins C and D was demonstrated using the ferric reducing antioxidant power (FRAP) assay. Additionally, at 1.25 μM, actinosporins C and D showed a significant antioxidant and protective capacity from the genomic damage induced by hydrogen peroxide in the human promyelocytic (HL-60) cell line.
Similarity between Flavonoid Biosynthetic Enzymes and Flavonoid Protein Targets Captured by Three-Dimensional Computing Approach
Publisher: Georg Thieme Verlag KG
Date: 26-02-2015
Abstract: Natural products are made by nature through interaction with biosynthetic enzymes. They also exert their effect as drugs by interaction with proteins. To address the question "Do biosynthetic enzymes and therapeutic targets share common mechanisms for the molecular recognition of natural products?", we compared the active site of five flavonoid biosynthetic enzymes to 8077 ligandable binding sites in the Protein Data Bank using two three-dimensional-based methods (SiteAlign and Shaper). Virtual screenings efficiently retrieved known flavonoid targets, in particular protein kinases. A consistent performance obtained for variable site descriptions (presence/absence of water, variable boundaries, or small structural changes) indicated that the methods are robust and thus well suited for the identification of potential target proteins of natural products. Finally, our results suggested that flavonoid binding is not primarily driven by shape, but rather by the recognition of common anchoring points.
Pseudoceramines A–D, new antibacterial bromotyrosine alkaloids from the marine sponge Pseudoceratina sp.
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C1OB05581J
Abstract: Bioassay-guided fractionation of the CH(2)Cl(2)/MeOH extract of the Australian marine sponge Pseudoceratina sp. resulted in the purification of four new bromotyrosine alkaloids, pseudoceramines A-D (1-4), along with a known natural product, spermatinamine (5). The structures of 1-5 were determined by spectroscopic methods. Pseudoceramines A (1) and B (2) feature a rare bromotyrosyl-spermine-bromotyrosyl sequence, and pseudoceramine C (3) is the first ex le of bromotyrosine coupled with an N-methyl derivative of spermidine. Compounds 1-5 were screened for inhibition of toxin secretion by the type III secretion (T3S) pathway in Yersinia pseudotuberculosis. Compounds 2 and 5 inhibited secretion of the Yersinia outer protein YopE (IC(50) = 19 and 6 μM, respectively) and the enzyme activity of YopH (IC(50) = 33 and 6 μM, respectively).
Genome-based mining of new antimicrobial meroterpenoids from the phytopathogenic fungus Bipolaris sorokiniana strain 11134
Publisher: Springer Science and Business Media LLC
Date: 26-03-2020
Antibacterial and antifungal screening of natural products sourced from Australian fungi and characterisation of pestalactams D-F
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.PHYTOCHEM.2015.12.014
Abstract: Eighteen natural products sourced from Australian micro- or macro-fungi were screened for antibacterial and antifungal activity. This focused library was comprised of caprolactams, polyamines, quinones, and polyketides, with additional large-scale isolation studies undertaken in order to resupply previously identified compounds. Chemical investigations of the re-fermented culture from the endophytic fungus Pestalotiopsis sp. yielded three caprolactam analogues, pestalactams D-F, along with larger quantities of the known metabolite pestalactam A, which was methylated using diazomethane to yield 4-O-methylpestalactam A. The chemical structures of the previously undescribed fungal metabolites were determined by analysis of 1D/2D NMR and MS data. The structure of 4-O-methylpestalactam A was confirmed following single crystal X-ray diffraction analysis. The antibacterial and antifungal activity of all compounds was assessed, which identified three compounds, (1S,3R)-austrocortirubin, (1S,3S)-austrocortirubin, and 1-deoxyaustrocortirubin with mild activity (100 μM) against Gram-positive isolates and one compound, 2-hydroxy-6-methyl-8-methoxy-9-oxo-9H-xanthene-1-carboxylic acid, with activity against Cryptococcus neoformans and Cryptococcus gattii at 50 μM.
Unequivocal 13C NMR assignment of cyclohexadienyl rings in bromotyrosine‐derived metabolites from marine sponges
Publisher: Wiley
Date: 10-09-2012
DOI: 10.1002/MRC.3868
Abstract: Bromotyrosine-derived compounds are commonly isolated from Verongida sponges and are a major class of marine natural products. Here we report on the unequivocal (13)C NMR assignment of the brominated carbons at positions C-2 and C-4 of the cyclohexadiene ring, two carbons whose resonances are often incorrectly assigned. Interpretation of HMBC data acquired for a series of known bromotyrosine analogues, which included ianthesine E(1), aerothionin (2), 11-hydroxyaerothionin (3), and 11,19-dideoxyfistularin-3 (4), allowed us to unequivocally assign the carbons in question, C-2 and C-4, through the observance of unique HMBC correlations from the C-1 hydroxyl proton. Here we present the complete 2D NMR data sets recorded in DMSO-d(6) for 2-4 that were used to confirm the assignment and establish the working model. Using this model, a survey of the literature revealed that many members of this structure class had been wrongly assigned. This paper serves to reassign those compounds whose (13)C NMR assignment at positions C-2 and C-4 of the cyclohexadiene ring should be reversed.
Synthesis of 5-methylfuro[3,2-c]quinolin-4(5H)-one via palladium-catalysed cyclisation of N-(2-iodophenyl)-N-methyl-3-furamide
Publisher: Elsevier BV
Date: 10-2006
Cytotoxic Cyclic Depsipeptides from the Australian Marine Sponge Neamphius huxleyi
Publisher: American Chemical Society (ACS)
Date: 06-12-2012
DOI: 10.1021/NP3006474
Abstract: Three new cyclic depsipeptides, ne hamides B (2), C (3), and D (4), were isolated from the Australian sponge Ne hius huxleyi. The planar structural characterization of these molecules was elucidated using 2D NMR experiments and ESI-FTICR-MS(n). Their configurations were determined by Marfey's method and J-based NMR analysis. These new metabolites inhibited the growth of human cell lines (A549, HeLa, LNCaP, PC3, and NFF) with IC(50) values ranging from 88 to 370 nM. However, ne hamide D causes A549 cell proliferation at subcytotoxic doses and should be treated cautiously as a cytotoxic compound.
Drug-like Properties: Guiding Principles for the Design of Natural Product Libraries
Publisher: American Chemical Society (ACS)
Date: 28-12-2011
DOI: 10.1021/NP200687V
Abstract: While natural products or their derivatives and mimics have contributed around 50% of current drugs, there has been no approach allowing front-loading of chemical space compliant with lead- and drug-like properties. The importance of physicochemical properties of molecules in the development of orally bioavailable drugs has been recognized. Classical natural product drug discovery has only been able to undertake this analysis retrospectively after compounds are isolated and structures elucidated. The present approach addresses front-loading of both extracts and subsequent fractions with desired physicochemical properties prior to screening for drug discovery. The physicochemical profiles of natural products active against two neglected disease targets, malaria and African trypanosomiasis, are presented based on this strategy. This approach can ensure timely development of natural product leads at a hitherto unachievable rate.
Unique Polybrominated Hydrocarbons from the Australian Endemic Red Alga Ptilonia australasica
Publisher: American Chemical Society (ACS)
Date: 23-02-2016
DOI: 10.1021/ACS.JNATPROD.5B00989
Abstract: The red alga Ptilonia australasica is endemic to Australian temperate waters. Chemical investigation of P. australasica led to the identification of four new polybrominated compounds, ptilones A-C (1-3) and australasol A (4). Their planar structures were established by extensive NMR and MS analyses. The low H/C ratio and the presence of a large number of heteroatoms made the structure elucidation challenging. The absolute configurations of 1, 2, and 4 were determined by quantum chemical ECD calculations employing time-dependent density functional theory. Ptilones A-C (1-3) show unique 4-ethyl-5-methylenecyclopent-2-enone (1 and 2) and 2-methyl-6-vinyl-4H-pyran-4-one (3) skeletons not previously reported in algal metabolites. Ptilone A displayed the most potent cytotoxicity against the human prostate cancer PC3 cells with an IC50 value of 0.44 μM and induced the PC3 cell cycle arrest in the G0/G1 phase.
Adociasalfates 1, 7, and 8: New bioactive hexaprenoid hydroquinones from the marine sponge Adocia sp.
Publisher: American Chemical Society (ACS)
Date: 07-1999
DOI: 10.1021/JO990404D
Abstract: Adociasulfate 1 (1), adociasulfate 7 (2), and adociasulfate 8 (3), which are inhibitors of proton pump activity in hen bone-derived membrane vesicles, were isolated from an extract of the sponge Adocia sp. (Chalinidae). Structure elucidation by 2D-NMR spectroscopy revealed that they are novel hexaprenoid hydroquinone sulfates.
Aporphine Alkaloids from the Chinese Tree Neolitsea Aurata Var. Paraciculata
Publisher: SAGE Publications
Date: 03-2007
DOI: 10.1177/1934578X0700200306
Abstract: Three new oxygenated noraporphine alkaloids were isolated from the bark of the Chinese tree Neolitsea aurata var. paraciculata. The new compounds, (+)-11-methoxynorcassythicine, (+)-11-methoxynorneolitsine, (+)-11-methoxynorboldine, were isolated along with eight known aporphine alkaloids, hernovine, ovigerine, N-methylovigerine, 10-O-methylhernovine, lindcarpine, N,O-dimethylhernovine, laurolitsine and nandigerine. Their structures were determined by 1D and 2D NMR spectroscopy. This is the first report of chemical constituents from N. aurata var. paraciculata.
Synthese stereoisomerer Pinanthromboxane und Evaluation der Verbindungen als Plättchenaggregationsinhibitoren
Publisher: Wiley
Date: 05-05-1983
Comprehensive TCM molecular networking based on MS/MS in silico spectra with integration of virtual screening and affinity MS screening for discovering functional ligands from natural herbs
Publisher: Springer Science and Business Media LLC
Date: 24-06-2019
DOI: 10.1007/S00216-019-01962-4
Abstract: Accessing the rich source of compounds from natural herbs for use in the pharmaceutical industry using conventional bioassay-based screening platforms has low efficiency and is cost-prohibitive. In this study, we developed a new method involving traditional Chinese medicine (TCM) molecular networking and virtual screening coupled with affinity mass spectrometry (MN/VS-AM) for the efficient discovery of herb-derived ligands. The in silico MS/MS fragmentation database (ISDB) generated by molecular networking of TCM can rapidly identify compounds in complex herb extracts and perform compound activity mapping. Additionally, the pre-virtual screening conveniently includes candidate herbs with potential bioactivity, while affinity MS screening completely eliminates the requirement for a tedious pure compound preparation at the initial screening phase. After applying this approach, two types of compounds, isoamylene flavanonols and 20(s)-protopanoxadio saponins, which were confirmed to interact with the small GTPase of Ras, were successfully identified from a dozen anti-cancer TCM herbs. The results demonstrate that the modified screening strategy dramatically improved the accuracy and throughput sensitivity of ligand screening from herbal extracts. Graphical abstract.
Linckosides enhance proliferation and induce morphological changes in human olfactory ensheathing cells.
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.MCN.2016.06.005
Abstract: Linckosides are members of the steroid glycoside family isolated from the starfish Linckia laevigata. These natural compounds have notable neuritogenic activity and synergistic effects on NGF-induced neuronal differentiation of PC12 cells. Neurogenic factors or molecules that are able to mimic their activities are known to be involved in the survival, proliferation and migration of neurons and glial cells however how glial cells respond to specific neurogenic molecules such as linckosides has not been investigated. This study aimed to examine the effect of three different linckosides (linckoside A, B and granulatoside A) on the morphological properties, proliferation and migration of human olfactory ensheathing cells (hOECs). The proliferation rate after all the treatments was higher than control as detected by MTS assay. Additionally, hOECs displayed dramatic morphological changes characterized by a higher number of processes after linckoside treatment. Interestingly changes in microtubule organization and expression levels of some early neuronal markers (GAP43 and βIII-tubulin) were also observed. An increase in the phosphorylation of ERK 1/2 after addition of the compounds suggests that this pathway may be involved in the linckoside-mediated effects particularly those related to morphological changes. These results are the first description of the stimulating effects of linckosides on hOECs and raise the potential for this natural compound or its derivatives to be used to regulate and enhance the therapeutic properties of OECs, particularly for cell transplantation therapies.
Lignans from the Australian Endemic Plant Austrobaileya scandens
Publisher: American Chemical Society (ACS)
Date: 23-05-2016
DOI: 10.1021/ACS.JNATPROD.5B00988
Abstract: The sole species of the vascular plant family Austrobaileyaceae, Austrobaileya scandens, is endemic to the tropical rainforest of northeastern Queensland, Australia. A single lead-like enhanced fraction of A. scandens showed potent inhibition against human prostate cancer PC3 cells. Chemical investigation of this plant resulted in the isolation of two new aryltetralin lignans, austrobailignans 8 and 9 (1 and 2), and the synthetic compound nicotlactone B (3), newly identified as a natural product together with nine known lignans (4-12). Their structures were established on the basis of spectroscopic analyses. Absolute configurations of the new compounds were determined by quantum chemical electronic circular dichroism (ECD) calculations employing time-dependent density functional theory. The ECD calculations were also used to assign the absolute configuration of marphenol K (4) and revise the absolute configuration of kadsurindutin C (20). Ten out of the 12 isolated compounds inhibited the growth of PC3 cells with IC50 values ranging from micromolar to nanomolar. Marphenol A (5) was found for the first time to induce apoptosis and arrest the S cell cycle phase of PC3 cells.
Tropane alkaloids from Darlingia darlingiana
Publisher: Elsevier BV
Date: 10-1999
A study of the binding requirements of calyculin A and dephosphonocalyculin A with PP1, development of a molecular recognition model for the binding interactions of the okadaic acid class of compounds
Publisher: Elsevier BV
Date: 2001
DOI: 10.1016/S0928-0987(00)00116-0
Abstract: The interactions of the okadaic acid class of compounds, with special emphasis on the solution structures of calyculin A and dephosphonocalyculin A with PP1 are reported. After examination of the interactions of all docked structures, a receptor based pharmacophore model for the interactions of the protein phosphatase inhibitors has been developed. Calyculin A or dephosphonocalyculin A can interact with the enzyme in either a manner similar to the reported crystal structure, or in an extended form. The inhibitors require two essential regions interacting with the hydrophobic region and the central metal binding regions of the enzyme. This simplified model is consistent with previously published models of the okadaic acid class of compounds with PP1.
Structural Elucidation of a Novel Scalarane Derivative by Using High-Field (14.1T) N.M.R. Spectroscopy
Publisher: CSIRO Publishing
Date: 1991
DOI: 10.1071/CH9910995
Abstract: A novel scalarane derivative (2) has been isolated from the marine sponge Carteriospongia foliascens. A complete assignment of the 1H and 13C n.m.r. spectra of (2) was achieved by using cosy-90, 1H-detected 1H/13C correlation (HMQC sequence) and 1H-detected long-range 1H/13C correlation (HMBC sequence) experiments, all measured at 600 MHz. The assignment of stereochemistry at C4 was supported by a ROESY spectrum.
MONO-ALPHA-CARBAMOYLETHYLTHIO-SUBSTITUTED PYRAZOLO[3,4-D]PYRIMIDINES - THE POSITION OF SUBSTITUTION
Publisher: CSIRO Publishing
Date: 1991
DOI: 10.1071/CH9910753
Abstract: Pyrazolo [3,4-d] pyrimidines are a general class of compounds which exhibit adenosine receptor affinity. One particular compound, α-{6-(1α-carbamoylethylthio)-1-phenylpyrazolo-[3,4-d]pyrimidin-4-ylthio} propionamide (1a), has been shown to have antagonist activity an order of magnitude greater than theophylline at the A1 adenosine receptor. The synthesis, structural elucidation by n.m.r. spectroscopy, and adenosine receptor affinity of the mono-α- carbamoylethylthio analogue is now reported.
Australian biodiversity via its plants and marine organisms. A high-throughput screening approach to drug discovery
Publisher: Walter de Gruyter GmbH
Date: 2002
Abstract: High-throughput screening (HTS) of extracts of Australian plants and marine organisms commenced in our laboratory in 1994. The biota collections commenced in late 1993. The collection has in excess of 30 000 biota s les including over 16 000 biota s les of vascular plants, algae, and macro fungi from Queensland, and over 4000 marine invertebrates from Australian waters. The plant collection represents ∼9 % of the world species ersity of higher plants, with representation from 73 % of the world's plant families. The marine collection contains ∼10 % of the world ersity of sponges, ∼10 % of the world ersity of ascidians, and ∼5 % of the world ersity of soft corals and gorgonians. The lecture will highlight some of the advances to knowledge about Australian bio ersity as a result of the HTS project, discuss drug discovery using HTS, and give some ex les of the chemistry arising from the screening of the extracts.
Eudistomin V, a New β-Carboline from the Australian Ascidian Pseudodistoma aureum
Publisher: American Chemical Society (ACS)
Date: 24-06-1998
DOI: 10.1021/NP9800452
Alkaloids from the Australian Rainforest Tree Ochrosia moorei
Publisher: American Chemical Society (ACS)
Date: 16-04-2008
DOI: 10.1021/NP070655E
Abstract: High-throughput screening of a plant and marine invertebrate extract library to find natural products that down-regulate expression of pro-inflammatory genes associated with the glucocorticoid receptor ligand complex led to the identification of bioactive CH2Cl 2 extracts from stems and leaves of the Queensland tree Ochrosia moorei. Bioassay-guided purification of the stem extract enabled the isolation of four alkaloids including two new compounds, ochrosamines A (1) and B (2), and the known compounds ellipticine (3) and 9-methoxyellipticine (4). The leaf extract also afforded 3 and 4 as well as apparicine (5) and desoxycordifoline (6). The structures of the two new compounds were assigned from interpretation of 2D NMR and high-resolution ESIMS data. Ellipticine and 9-methoxyellipticine were the most active components, and both displayed IC 50 values of 90 microM. Apparicine and desoxycordifoline were only very weakly active, and ochrosamines A and B were inactive.
(+)-7-Bromotrypargine: an antimalarial β-carboline from the Australian marine sponge Ancorina sp.
Publisher: Elsevier BV
Date: 2010
Petrosamine B, an Inhibitor of the Helicobacter pylori Enzyme Aspartyl Semialdehyde Dehydrogenase from the Australian Sponge Oceanapia sp.
Publisher: American Chemical Society (ACS)
Date: 05-2005
DOI: 10.1021/NP049595S
Abstract: Bioassay-guided fractionation of the MeOH extract of the sponge Oceanapia sp. using the Helicobacter pylori enzyme, aspartyl semialdehyde dehydrogenase, ASD, to detect antibacterial activity, led to the isolation of a new pyridoacridine alkaloid, petrosamine B (1). Petrosamine B is a bright blue compound that is sparingly soluble in many organic solvents. The structure of 1 was determined from detailed NMR studies performed in TFA/D2O. Petrosamine B was found to be a weak inhibitor of ASD with an IC50 of 306 microM.
Characterization of the neurotoxic constituents of Conus geographus (L) venom
Publisher: Elsevier BV
Date: 12-1977
3-Hydroxy-4-methoxyphenethylamine, the cardioactive constituent of a soft coral
Publisher: Springer Science and Business Media LLC
Date: 05-1981
DOI: 10.1007/BF01986157
Abstract: Pancreatoblastoma is a rare paediatric malignant neoplasm. The treatment of choice is complete surgical resection. However, it is often unresectable due to its large size, local infiltration or distant metastasis. Since the condition is rare, there is currently no standard treatment regimen. We outline the case of a 4-year-old child who presented with abdominal pain and distention, together with an enlarged liver and elevated serum α-fetoprotein levels. Imaging studies showed the presence of an abnormal pancreatic tumour and multiple nodular lesions in the liver, the biopsies from which led to a diagnosis of pancreatoblastoma. In this case, the patient received cycles of neoadjuvant chemotherapy, combining cisplatin and doxorubicin. The patient subsequently underwent scheduled surgery in which the primary pancreatic lesion was resected, obtaining a circumscribed and nodular specimen measuring 7 × 6 cm and weighing 150 g. Given the extent of the metastasis, the child is currently awaiting a liver transplant.
The mechanism of cleavage of Evans chiral auxiliaries by LiOOH: origins of the different regioselectivities obtained with LiOH, LiOOH, LiOBn and LiSBn
Publisher: CSIRO Publishing
Date: 2023
DOI: 10.1071/CH23086
Synthesis of antitrypanosomal 1,2-dioxane derivatives based on a natural product scaffold
Publisher: Elsevier BV
Date: 08-2011
Spermatinamine, the first natural product inhibitor of isoprenylcysteine carboxyl methyltransferase, a new cancer target
Publisher: Elsevier BV
Date: 12-2007
DOI: 10.1016/J.BMCL.2007.10.021
Abstract: Isoprenylcysteine methyltransferase (Icmt) catalyzes the carboxyl methylation of oncogenic proteins in the final step of a series of post-translational modifications. The inhibition of Icmt provides an attractive and novel anticancer target. A natural product high-throughput screening c aign was conducted to discover inhibitors of Icmt. The Australian marine sponge, Pseudoceratina sp., yielded spermatinamine, a novel alkaloid with a bromotyrosyl-spermine-bromotyrosyl sequence, as the bioactive constituent. Its structure was determined by 1D and 2D NMR spectroscopy. Spermatinamine is the first natural product inhibitor of Icmt.
The Identification of Bioactive Natural Products by High Throughput Screening (HTS)
Publisher: Elsevier
Date: 2010
Fluorine Is a Major Constituent of the Marine Sponge Halichondria moorei
Publisher: American Association for the Advancement of Science (AAAS)
Date: 30-11-1979
DOI: 10.1126/SCIENCE.206.4422.1108
Abstract: Fluorine constitutes about 10 percent of the dry weight of the marine sponge Halichondria moorei. The fluorine occurs as potassium fluorosilicate, which is a potent anti-inflammatory agent. A closely related sponge living in the same habitat does not contain any fluorine. The habitat was found to be free of fluorine except for the small amount naturally present in seawater.
1-Methylisoguanosine, a pharmacologically active agent from a marine sponge
Publisher: American Chemical Society (ACS)
Date: 09-1980
DOI: 10.1021/JO01308A015
Structural Insights into the Molecular Basis of the Ligand Promiscuity
Publisher: American Chemical Society (ACS)
Date: 05-09-2012
DOI: 10.1021/CI300196G
Abstract: Selectivity is a key factor in drug development. In this paper, we questioned the Protein Data Bank to better understand the reasons for the promiscuity of bioactive compounds. We assembled a data set of >1000 pairs of three-dimensional structures of complexes between a "drug-like" ligand (as its physicochemical properties overlap that of approved drugs) and two distinct "druggable" protein targets (as their binding sites are likely to accommodate "drug-like" ligands). Studying the similarity between the ligand-binding sites in the different targets revealed that the lack of selectivity of a ligand can be due (i) to the fact that Nature has created the same binding pocket in different proteins, which do not necessarily have otherwise sequence or fold similarity, or (ii) to specific characteristics of the ligand itself. In particular, we demonstrated that many ligands can adapt to different protein environments by changing their conformation, by using different chemical moieties to anchor to different targets, or by adopting unusual extreme binding modes (e.g., only apolar contact between the ligand and the protein, even though polar groups are present on the ligand or at the protein surface). Lastly, we provided new elements in support to the recent studies which suggest that the promiscuity of a ligand might be inferred from its molecular complexity.
Synthesis and antimalarial evaluation of amide and urea derivatives based on the thiaplakortone A natural product scaffold
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C4OB01849D
Abstract: A series of amide and urea analogues based on the thiaplakortone A natural product scaffold were synthesised and screened for in vitro antimalarial activity.
Antimalarial Bromotyrosine Derivatives from the Australian Marine Sponge Hyattella sp.
Publisher: American Chemical Society (ACS)
Date: 12-05-2010
DOI: 10.1021/NP900834G
Abstract: A drug discovery program aimed at identifying new antimalarial leads from a prefractionated natural product library has resulted in the identification of a new bromotyrosine alkaloid, psammaplysin G (1), along with the previously isolated compound, psammaplysin F (2). When tested against two different strains of the parasite Plasmodium falciparum (Dd2 and 3D7), 2 displayed IC(50) values of 1.4 and 0.87 microM, respectively, while 1 showed 98% inhibition at 40 microM against the chloroquine-resistant (Dd2) strain of P. falciparum.
Total synthesis of thiaplakortone a: derivatives as metabolically stable leads for the treatment of malaria.
Publisher: American Chemical Society (ACS)
Date: 02-01-2013
DOI: 10.1021/ML400447V
Longithorones J and K, Two New Cyclofarnesylated Quinone Derived Metabolites from the Australian Ascidian Aplidium longithorax
Publisher: American Chemical Society (ACS)
Date: 11-11-1998
DOI: 10.1021/NP980275G
A systems approach using OSMAC, Log P and NMR fingerprinting: An approach to novelty
Publisher: Elsevier BV
Date: 12-2017
TCM, brain function and drug space
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C5NP00049A
Abstract: This article reviews 84 major bioactive compounds from 15 selected traditional Chinese medicines targeting neurodegenerative diseases. The physicochemical property comparison of these TCM compounds and current drugs and candidates for the treatment of Parkinson's and Alzheimer's disease are analysed.
Clavatadines C−E, Guanidine Alkaloids from the Australian Sponge Suberea clavata
Publisher: American Chemical Society (ACS)
Date: 20-04-2009
DOI: 10.1021/NP8008013
Abstract: Three new marine alkaloids, clavatadines C-E (1-3), together with the three known compounds aerophobin 1 (4), purealdin L (5), and aplysinamisine II (6) were isolated from extracts of the sponge Suberea clavata by bioassay-guided fractionation using a serine protease factor XIa assay. Their structures were determined by 1D and 2D NMR spectroscopy. Compounds 1-6 exhibited weak inhibition of factor XIa.
Eco-Taxonomic Insights into Actinomycete Symbionts of Termites for Discovery of Novel Bioactive Compounds
Publisher: Springer Berlin Heidelberg
Date: 2015
DOI: 10.1007/10_2014_270
Abstract: Termites play a major role in foraging and degradation of plant biomass as well as cultivating bioactive microorganisms for their defense. Current advances in "omics" sciences are revealing insights into function-related presence of these symbionts, and their related biosynthetic activities and genes identified in gut symbiotic bacteria might offer a significant potential for biotechnology and biodiscovery. Actinomycetes have been the major producers of bioactive compounds with an extraordinary range of biological activities. These metabolites have been in use as anticancer agents, immune suppressants, and most notably, as antibiotics. Insect-associated actinomycetes have also been reported to produce a range of antibiotics such as dentigerumycin and mycangimycin. Advances in genomics targeting a single species of the unculturable microbial members are currently aiding an improved understanding of the symbiotic interrelationships among the gut microorganisms as well as revealing the taxonomical identity and functions of the complex multilayered symbiotic actinofloral layers. If combined with target-directed approaches, these molecular advances can provide guidance towards the design of highly selective culturing methods to generate further information related to the physiology and growth requirements of these bioactive actinomycetes associated with the termite guts. This chapter provides an overview on the termite gut symbiotic actinoflora in the light of current advances in the "omics" science, with ex les of their detection and selective isolation from the guts of the Sunshine Coast regional termite Coptotermes lacteus in Queensland, Australia.
7 ',8 '-Dihydroobolactone, a typanocidal alpha-pyrone from the rainforest tree Cryptocarya obovata
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.BMCL.2010.05.091
Abstract: Mass-directed isolation of the CH(2)Cl(2)/MeOH extract from the leaves of Cryptocarya obovata resulted in the purification of a new trypanocidal alpha-pyrone, 7',8'-dihydroobolactone (1). The chemical structure of 1 was determined by 1D/2D NMR, MS and CD data analysis. 7',8'-Dihydroobolactone was shown to inhibit Trypanosoma brucei brucei with an IC(50) of 2.8 microM.
Psammaplysin H, a new antimalarial bromotyrosine alkaloid from a marine sponge of the genus Pseudoceratina
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.BMCL.2010.11.081
Abstract: Mass-directed isolation of the CH(2)Cl(2)/CH(3)OH extract from a marine sponge of the genus Pseudoceratina resulted in the purification of a new antimalarial bromotyrosine alkaloid, psammaplysin H (1), along with the previously isolated analogs psammaplysins G (2) and F (3). The structure of 1 was elucidated following 1D and 2D NMR, and MS data analysis. All compounds were tested in vitro against the 3D7 line of Plasmodium falciparum and mammalian cell lines (HEK293 and HepG2), with 1 having the most potent (IC(50) 0.41μM) and selective (>97-fold) antimalarial activity.
Genome-Inspired Chemical Exploration of Marine FungusAspergillus fumigatusMF071
Publisher: MDPI AG
Date: 06-07-2020
DOI: 10.3390/MD18070352
Abstract: The marine-derived fungus Aspergillus fumigatus MF071, isolated from sediment collected from the Bohai Sea, China, yielded two new compounds 19S,20-epoxy-18-oxotryprostatin A (1) and 20-hydroxy-18-oxotryprostatin A (2), in addition to 28 known compounds (3–30). The chemical structures were established on the basis of 1D, 2D NMR and HRESIMS spectroscopic data. This is the first report on NMR data of monomethylsulochrin-4-sulphate (4) and pseurotin H (10) as naturally occurring compounds. Compounds 15, 16, 20, 23, and 30 displayed weak antibacterial activity (minimum inhibitory concentration: 100 μg/mL). Compounds 18 and 19 exhibited strong activity against S. aureus (minimum inhibitory concentration: 6.25 and 3.13 μg/mL, respectively) and E. coli (minimum inhibitory concentration: 6.25 and 3.13 μg/mL, respectively). A genomic data analysis revealed the putative biosynthetic gene clusters ftm for fumitremorgins, pso for pseurotins, fga for fumigaclavines, and hel for helvolinic acid. These putative biosynthetic gene clusters fundamentally underpinned the enzymatic and mechanistic function study for the biosynthesis of these compounds. The current study reported two new compounds and biosynthetic gene clusters of fumitremorgins, pseurotins, fumigaclavines and helvolinic acid from Aspergillus fumigatus MF071.
1-Phenylpyrazolo[3,4- d ]pyrimidines; structure–activity relationships for C6 substituents at A 1 and A 2A adenosine receptors
Publisher: Elsevier BV
Date: 11-2000
DOI: 10.1016/S0968-0896(00)00190-5
Abstract: Substitution of I-phenylpyrazolo[3,4-d]pyrimidines at C6 with N-alkyl-2-thiopropionamide groups has resulted in a series of 18 compounds which have been evaluated for binding at A1 and A2A adenosine receptors. Introduction of an N-ethyl group gave increased affinity at both A1 and A2A receptors for the amino compound 7b compared to the primary amide 7a. An additional hydrophobic pocket exists for substituents on the amide. This pocket allows an N-ethyl group for increased affinity at both A1 and A2A receptors, allows larger alkyl groups at A2A receptors but not at A1 receptors and there is an H-bond interaction requiring one H-bond donor. Molecular modeling studies have also enabled a proposal of the amino acid residues involved in ligand binding at both the A1 and A2A receptors.
Synthesis of a pyrimidine by elimination of nitrogen from a triazolo[4,5-d]pyrimidine
Publisher: Elsevier BV
Date: 1990
Antiplasmodial activity of the natural product compounds alstonine and himbeline
Publisher: Elsevier BV
Date: 08-2021
A Benzylisoquinoline Alkaloid from Doryphora sassafras
Publisher: American Chemical Society (ACS)
Date: 17-11-2001
DOI: 10.1021/NP010132L
Abstract: Chemical investigation of the Australian rainforest plant Doryphora sassafras has resulted in the isolation of a new natural product, 2-methyl-1-(p-methoxybenzyl)-6,7-methylenedioxyisoquinolinium chloride (1). The iodide salt of compound 1 has previously been synthesized but only partially characterized. This paper reports the full spectroscopic characterization of 1 by MS, IR, UV, and NMR data.
Prenylated Dihydrochalcones from Boronia bipinnata that Inhibit the Malarial Parasite Enzyme Target Hemoglobinase II
Publisher: American Chemical Society (ACS)
Date: 29-07-2008
DOI: 10.1021/NP8002707
Abstract: High-throughput screening of a plant and marine invertebrate extract library to find natural products that inhibit the malarial parasite enzyme target hemoglobinase II led to the isolation of two new active prenylated chalcones, bipinnatones A (1) and B (2), from aerial parts of the Queensland shrub Boronia bipinnata. Their structures were assigned from interpretation of 2D NMR and high-resolution ESIMS data. Compounds 1 and 2 inhibited hemoglobinase II with IC 50 values of 64 and 52 microM, respectively.
Actinomycete Metabolome Induction/Suppression with N-Acetylglucosamine
Publisher: American Chemical Society (ACS)
Date: 29-03-2017
DOI: 10.1021/ACS.JNATPROD.6B00673
Abstract: The metabolite profiles of three sponge-derived actinomycetes, namely, Micromonospora sp. RV43, Rhodococcus sp. RV157, and Actinokineospora sp. EG49 were investigated after elicitation with N-acetyl-d-glucosamine.
Perspicamides A and B, Quinolinecarboxylic Acid Derivatives from the Australian Ascidian Botrylloides perspicuum
Publisher: American Chemical Society (ACS)
Date: 23-11-2005
DOI: 10.1021/NP0502239
Abstract: Two novel quinoline-2-carboxylic acid derivatives, perspicamides A (2) and B (3), were isolated from the Australian ascidian Botrylloides perspicuum. Extraction of the freeze-dried ascidian with methanol and purification of the extract by C18 MPLC followed by repeated C18 HPLC yielded the new compounds 2 and 3 as well as the known compounds botryllamides A-C (4-6). The structures of 2 and 3 were determined from analysis of 2D NMR spectra.
1-Phenylpyrazolo[3,4-d]pyrimidines as adenosine antagonists: the effects of substituents at C4 and C6
Publisher: Elsevier BV
Date: 02-1997
DOI: 10.1016/S0968-0896(96)00240-4
Abstract: Forty-two 1-phenyl-pyrazolo[3,4-d]pyrimidines substituted at C6 with thioethers containing distal amide substituents and substituted at C4 with thiol, thiomethyl or amino were synthesized and tested for adenosine A1 and A2a receptor binding. Compared with a thiol at C4, both S-methylation and conversion to an amino resulted in increased affinity at both receptors with the C4 amino compounds having the highest affinity. The C-4 region of the receptor consists of an alkyl pocket containing a hydrogen-bonding site. The study established that for high affinity at both the A1 and A2a adenosine receptors the distal amide should be separated from the C6 thiol by only one carbon. In this study, 2'-(4-amino-1-phenylpyrazolo[3,4-d]pyrimidin-6-ylthio)-N-ethyl- ethanamide (4b) had the highest affinity at the A1 receptor with a Ki of 12.1 nM while 2'-(4-amino-1-phenylpyrazolo[3,4-d]pyrimidin-6-ylthio)ethanamid e (4a) had the highest affinity at the A2a receptor with a Ki of 44.9 nM.
Development of an HPLC-based guanosine monophosphate kinase assay and application to Plasmodium vivax guanylate kinase
Publisher: Elsevier BV
Date: 06-2019
Antimalarial Activity of Azafluorenone Alkaloids from the Australian Tree Mitrephora diversifolia
Publisher: American Chemical Society (ACS)
Date: 10-07-2009
DOI: 10.1021/NP900247F
Abstract: Mass-directed isolation of the CH2Cl2/MeOH extract from the roots of the Australian tree Mitrephora ersifolia resulted in the purification of the new azafluorenone alkaloid 5,8-dihydroxy-6-methoxyonychine (1) together with the known natural product 5-hydroxy-6-methoxyonychine (2). The structures of 1 and 2 were determined by extensive 1D and 2D NMR and MS data analyses. Both compounds were isolated during a drug discovery program aimed at the identification of new antimalarial leads from a prefractionated natural product library. When tested against two different strains of the parasite Plasmodium falciparum (3D7 and Dd2), 2 displayed IC(50) values of 9.9 and 11.4 microM, respectively, while 1 showed minimal activity.
Further Acetylenic Acids from the Marine Sponge Xestospongia testudinaria
Publisher: American Chemical Society (ACS)
Date: 1991
DOI: 10.1021/NP50073A037
Comparing atom-based with residue-based descriptors in predicting binding site similarity: do backbone atoms matter?
Publisher: Future Science Ltd
Date: 10-2016
Abstract: Aim: We question the level of detail required in protein 3D-representation to detect site similarity which is relevant for polypharmacology prediction. Results: We modified the in-house program SiteAlign to replace generic pharmacophoric descriptors of cavity-lining amino acids by descriptors accounting for solvent exposure. Benchmarking the novel, atom-based, method (SiteAlign2) revealed no global improvement of performance. However, in the rare cases of no sequence or global structure similarities between the compared proteins, SiteAlign2 was more successful if backbone atoms are key determinants of ligand binding. Conclusion: SiteAlign suits the comparison of binding sites for close or distant homologs. SiteAlign2 provides a better insight into the physical model of site similarity between nonhomologs, but at the expense of an increased sensitivity to atomic coordinates.
Natural Products, Stylissadines A and B, Specific Antagonists of the P2X7 Receptor, an Important Inflammatory Target1
Publisher: American Chemical Society (ACS)
Date: 22-02-2007
DOI: 10.1021/JO062007Q
Abstract: The distribution of the P2X7 receptor in inflammatory cells suggests that P2X7 antagonists have a significant role to play in the treatment of inflammatory disease. We conducted a natural product high-throughput screening c aign to discover P2X7 receptor antagonists. The Australian marine sponge Stylissa flabellata yielded two new bisimidazo-pyrano-imidazole bromopyrrole ether alkaloids, stylissadines A (IC50 0.7 microM) and B (IC50 1.8 microM), as the specific bioactive constituents. The compounds inhibit BzATP-mediated pore formation in THP-1 cells. Also present in this extract was considerable nonspecific bioactivity in the hemeolysin specificity assay. A new pyrrole-imidazole alkaloid, konbu'acidin B, and the known pyrrole-imidazole alkaloids 4,5-dibromopalau'amine and massadine were also isolated and had nonspecific activity. ROESY and proton coupling constant data indicated that the stereochemistry at C12, C17, and C20 in 4,5-dibromopalau'amine should be revised to 12R, 17S, 20S. By analogy, the relative stereochemistry of palau'amine, 4-bromopalau'amine, styloguanidine, 3-bromostyloguanidine, and 2,3-dibromostyloguanidine should also be revised to 12R, 17S, 20S. Stylissadines A and B are the most potent natural product P2X7 antagonists to be isolated to date and provide a novel class of P2X7 receptor inhibitors. They are also the first ex les of tetrameric pyrrole-imidazole alkaloids.
Correction: The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C8NP90041H
Abstract: Correction for ‘The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research’ by James B. McAlpine et al. , Nat. Prod. Rep. , 2018, DOI: 10.1039/c7np00064b.
Potential of marine natural products against drug-resistant bacterial infections
Publisher: Elsevier BV
Date: 07-2019
The three binding domain model of adenosine receptors: molecular modeling aspects
Publisher: American Chemical Society (ACS)
Date: 1992
DOI: 10.1021/JM00080A002
Abstract: Using molecular modeling, adenosine receptor ligands were fitted together to maximize correlations between the three most important factors controlling binding to the receptor, namely steric, hydrophobic, and electrostatic complimentarily. Structure-activity relationships can be explained by three binding domains on the receptors. These are hydrophobic, aromatic, and ribose binding domains. We propose that the N6, C2, and C8 hydrophobic binding domains are not discreet but occupy the same region of the receptor.
The conserved acid binding domain model of inhibitors of protein phosphatases 1 and 2A: Molecular modelling aspects.
Publisher: Elsevier BV
Date: 06-1993
Actinophyllic Acid, a Potent Indole Alkaloid Inhibitor of the Coupled Enzyme Assay Carboxypeptidase U/Hippuricase from the Leaves of Alstonia actinophylla (Apocynaceae)
Publisher: American Chemical Society (ACS)
Date: 07-01-2005
DOI: 10.1021/JO048439N
Abstract: Bioassay-guided fractionation of the aqueous extract of the leaves of Alstonia actinophylla with use of a coupled enzyme assay, CPU/hippuricase, to detect carboxypeptidase U inhibitors led to the isolation of a novel indole alkaloid, actinophyllic acid (1). The structure of 1 was determined from detailed 2D NMR studies. Actinophyllic acid was found to be a potent inhibitor of the coupled enzyme assay with an IC(50) of 0.84 microM. Actinophyllic acid possesses a unique 2,3,6,7,9,13c-hexahydro-1H-1,7,8-(methanetriyloxymethano)pyrrolo[1',2':1,2]azocino[4,3-b]indole-8(5H)-carboxylic acid skeleton.
Naturally Occurring Cembranes from an Australian Sarcophyton Species
Publisher: American Chemical Society (ACS)
Date: 25-07-2002
DOI: 10.1021/NP010521F
Abstract: Naturally occurring cembranes 1-4 have been isolated from a Sarcophyton sp. These compounds have not previously been found to occur in nature but had been obtained as intermediates in a synthetic modification from tobacco. The absolute stereochemistries of 3 and 4 were determined. Compounds 1 and 2 inhibited the binding of [(3)H]8-cyclopentyl-1,3-dipropylxanthine to rat-brain adenosine A(1) receptors.
Bioaffinity Mass Spectrometry Screening using Droplet-Based Microfluidics
Publisher: Bentham Science Publishers Ltd.
Date: 16-12-2015
Latifolians A and B, Novel JNK3 Kinase Inhibitors from the Papua New Guinean Plant Gnetum latifolium
Publisher: American Chemical Society (ACS)
Date: 30-06-2005
DOI: 10.1021/NP049616I
Abstract: As part of our search for natural products active against the JNK3 kinase, two novel, charged benzylisoquinolines, latifolian A (1) and latifolian B (2), were isolated from the stem bark of the Papua New Guinean vine Gnetum latifolium. The planar structures were determined through detailed 2D NMR analysis. The relative configurations were assigned after examination of the ROESY data and through detailed molecular modeling studies.
Lipoxygenase inhibitors from the latex of Calotropis Procera
Publisher: Springer Science and Business Media LLC
Date: 09-03-2016
DOI: 10.1007/S12272-016-0725-9
Abstract: A radical-scavenging, guided phytochemical study of the latex of Calotropis Procera afforded five lignans (1-5), including a new one (4). The structural determination was accomplished using 1D- and 2D-NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), and correlation with known compounds. Among the isolated compounds, acylated lignans (3-5) showed stronger antioxidant activity than non-acylated derivatives (1,2). Anti-inflammatory activity was evaluated by determining the inhibitory potential against 5- and 15-lipoxygenase enzymes. The highest anti-inflammatory activity was observed in compound 4, with IC
Structure Determination of Pentacyclic Pyridoacridine Alkaloids from the Australian Marine Organisms Ancorina geodides and Cnemidocarpa stolonifera
Publisher: Wiley
Date: 23-06-2014
Advances in the development of imaging probes and aggregation inhibitors for alpha-synuclein
Publisher: Springer Science and Business Media LLC
Date: 04-10-2020
Meeting the Challenge 2: Identification of Potential Chemical Probes for Parkinson’s Disease from Ligusticum chuanxiong Hort Using Cytological Profiling
Publisher: American Chemical Society (ACS)
Date: 26-08-2022
DOI: 10.1021/ACSCHEMNEURO.1C00820
Abstract: Traditional Chinese medicine (TCM) has been around for thousands of years and is increasingly gaining popularity in the Western world to treat various complex disorders including the incurable neurodegenerative condition, Parkinson's Disease (PD). One of the many directions in recent studies of PD is utilizing the phenotypic assay, or cytological profiling, to evaluate the phenotypic changes of PD-implicated cellular components in patient-derived olfactory neuroepithelial (hONS) cells, upon treating the cells with extracts or pure compounds. To obtain small molecules for studies utilizing PD phenotyping assays,
Experimental Strategies for Functional Annotation and Metabolism Discovery: Targeted Screening of Solute Binding Proteins and Unbiased Panning of Metabolomes
Publisher: American Chemical Society (ACS)
Date: 16-01-2015
DOI: 10.1021/BI501388Y
The solution structures of calyculin A and dephosphonocalyculin A by NMR
Publisher: Elsevier BV
Date: 03-1999
DOI: 10.1016/S0960-894X(99)00066-9
Abstract: The NMR solution structure of calyculin A (1) in chloroform exhibits intramolecular interactions, resembling the original crystal structure. In methanol, calyculin A has the hydrogen bonding moieties solvent exposed. Dephosphonocalyculin A in chloroform resembles calyculin A in chloroform and the crystal structure of calyculin A. Dephosphonocalyculin A in methanol resembles calyculin A in methanol.
A Bastadin with Potent and Selective δ-Opioid Receptor Binding Affinity from the Australian Sponge Ianthella flabelliformis
Publisher: American Chemical Society (ACS)
Date: 19-05-2010
DOI: 10.1021/NP100010Z
Abstract: Three new bastadins, bastadin 25 (1), 15-O-sulfonatobastadin 11 (2), and bastadin 26 (3), were isolated from a MeOH extract of the Australian marine sponge Ianthella flabelliformis. Their structures were determined by interpretation of 1D and 2D NMR spectra and mass spectrometry. Bastadin 26 (3) showed potent affinity for the guinea pig delta-opioid receptors with a K(i) value of 100 nM. The other two bastadins had a 100-fold lower affinity. The three compounds were also tested for their affinity to guinea pig micro- and kappa-opioid receptors and shown to have either no affinity or only very weak affinity toward both of these opioid receptors.
Cytotoxic cardenolides from the latex of Calotropis procera
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.BMCL.2015.08.044
Abstract: Three new cardenolides (3, 9 and 10), along with eight known ones, were isolated from the latex of Calotropis procera. The structural determination was accomplished by the 1D- and 2D-NMR spectra as well as HRESIMS analysis. The growth inhibitory activity of the latex and its sub-fractions as well as isolated compounds was evaluated against human A549 and Hela cell lines. The results exhibited that latex had strong growth inhibitory activity with IC50s of (3.37 μM, A-549) and (6.45 μM, Hela). Among the four extracts (hexane, chloroform, ethyl acetate and aqueous), chloroform extract displayed the highest potential cytotoxic activity, with IC50s of (0.985 μM, A-549) and (1.471 μM, Hela). All the isolated compounds displayed various degrees of cytotoxic activity and the highest activity was observed by calactin (1) with IC50s values of (0.036 μM, A-549) and (0.083 μM, Hela). None of these isolated compounds exhibited good antimicrobial activity evaluated by determination of their MICs using the broth microdilution method against various infectious pathogens. The structure-activity relationships for cytotoxic activity were also discussed.
Antitrypanosomal pyridoacridine alkaloids from the Australian ascidian Polysyncraton echinatum
Publisher: Elsevier BV
Date: 05-2010
The role of arginine in interactions of microcystins with protein phosphatases 1 and 2a
Publisher: Elsevier BV
Date: 07-1992
The absolute stereochemistry and cytotoxicity of the ascidian-derived metabolite, longithorone J
Publisher: Informa UK Limited
Date: 12-2006
DOI: 10.1080/14786410601101811
Abstract: The absolute stereochemistry of longithorone J (1) from the ascidian Aplidium longithorax has been determined using the advanced Mosher method. Based on biosynthetic reasoning and chiroptical data comparison the absolute stereochemistry for longithorone K (2) was also assigned. Longithorone J was tested for cytotoxicity against the cell lines SHSY5Y, HEK293T and A549. Compound 1 showed minimal cytotoxicity towards the SHSY5Y and HEK293T cell lines.
Anticancer Activity of Zoanthids and the Associated Toxin, Palytoxin, against Ehrlich Ascites Tumor and P-388 Lymphocytic Leukemia in Mice
Publisher: Elsevier BV
Date: 02-1974
Abstract: With technological advancements and wider availability of multimodality imaging, incidental lesions are frequently identified in patients undergoing various imaging studies. We report here a case of multiloculated disseminated perineural or Tarlov cysts (TCs). The primary aim of our study was to (1) provide a comprehensive review of the clinical, imaging and histopathological features of TCs (2) to draw attention to the fact that multiple lumbo-sacral and dorsal TCs can produce nerve injuries and serious movement disturbances (3) to document the usefulness of the magnetic resonance imaging (MRI) and bone scan in noninvasive diagnosis and guiding management in such cases. These cysts are clearly identified by MR and computerized tomography imaging of the lumbosacral spine. However, there are no reports on the scintigraphic findings of TCs in literature. TCs are typically benign, asymptomatic lesions that can simply be monitored. Until date, no consensus exists about the best surgical strategy to be followed for their management.
A Phenotarget Approach for Identifying an Alkaloid Interacting with the Tuberculosis Protein Rv1466
Publisher: MDPI AG
Date: 05-03-2020
DOI: 10.3390/MD18030149
Abstract: In recent years, there has been a revival of interest in phenotypic-based drug discovery (PDD) due to target-based drug discovery (TDD) falling below expectations. Both PDD and TDD have their unique advantages and should be used as complementary methods in drug discovery. The PhenoTarget approach combines the strengths of the PDD and TDD approaches. Phenotypic screening is conducted initially to detect cellular active components and the hits are then screened against a panel of putative targets. This PhenoTarget protocol can be equally applied to pure compound libraries as well as natural product fractions. Here we described the use of the PhenoTarget approach to identify an anti-tuberculosis lead compound. Fractions from Polycarpa aurata were identified with activity against Mycobacterium tuberculosis H37Rv. Native magnetic resonance mass spectrometry (MRMS) against a panel of 37 proteins from Mycobacterium proteomes showed that a fraction from a 95% ethanol re-extraction specifically formed a protein-ligand complex with Rv1466, a putative uncharacterized Mycobacterium tuberculosis protein. The natural product responsible was isolated and characterized to be polycarpine. The molecular weight of the ligand bound to Rv1466, 233 Da, was half the molecular weight of polycarpine less one proton, indicating that polycarpine formed a covalent bond with Rv1466.
Structural Searching of Biosynthetic Enzymes to Predict Protein Targets of Natural Products
Publisher: Georg Thieme Verlag KG
Date: 03-11-2017
Abstract: Recently, we have demonstrated that site comparison methodology using flavonoid biosynthetic enzymes as the query could automatically identify structural features common to different flavonoid-binding proteins, allowing for the identification of flavonoid targets such as protein kinases. With the aim of further validating the hypothesis that biosynthetic enzymes and therapeutic targets can contain a similar natural product imprint, we collected a set of 159 crystallographic structures representing 38 natural product biosynthetic enzymes by searching the Protein Databank. Each enzyme structure was used as a query to screen a repository of approximately 10 000 ligandable sites by active site similarity. We report a full analysis of the screening results and highlight three retrospective ex les where the natural product validates the method, thereby revealing novel structural relationships between natural product biosynthetic enzymes and putative protein targets of the natural product. From a prospective perspective, our work provides a list of up to 64 potential novel targets for 25 well-characterized natural products.
Aplysinellamides A–C, Bromotyrosine-Derived Metabolites from an Australian Aplysinella sp. Marine Sponge
Publisher: American Chemical Society (ACS)
Date: 23-04-2014
DOI: 10.1021/NP500119E
Abstract: Mass-directed fractionation of an extract from the Australian marine sponge Aplysinella sp., from the Great Barrier Reef, resulted in the isolation of four new bromotyrosine derivatives, aplysinellamides A-C (1-3) and aplysamine-1-N-oxide (4), along with six known compounds (5-10). The structure elucidation of compounds 1-4 was based on their 1D and 2D NMR and MS spectroscopic data. Aplysamine-1 (6) increased the apolipoprotein E secretion from human CCF-STTG1 astrocytoma cells by 2-fold at the concentration of 30 μM.
Isolation and Total Synthesis of Stolonines A–C, Unique Taurine Amides from the Australian Marine Tunicate Cnemidocarpa stolonifera
Publisher: MDPI AG
Date: 22-07-2015
DOI: 10.3390/MD13074556
Guttiferones O and P, Prenylated Benzophenone MAPKAPK-2 Inhibitors from Garcinia solomonensis
Publisher: American Chemical Society (ACS)
Date: 14-08-2009
DOI: 10.1021/NP900246T
Abstract: Two prenylated benzophenones, guttiferones O (1) and P (2), were isolated from the stem bark of the Papua New Guinean plant Garcina solomonensis. The structures of these compounds and their relative configurations were determined by spectroscopic methods. Both compounds inhibited the phosphorylation of the synthetic biotinylated peptide substrate KKLNRTLSVA by the serine/threonine protein kinase MAPKAPK-2 with IC(50) values of 22.0 microM.
Total Synthesis of Clavatadine A
Publisher: American Chemical Society (ACS)
Date: 17-12-2014
DOI: 10.1021/NP500772U
Abstract: The first total synthesis of the potent and selective human blood coagulation factor XIa inhibitor clavatadine A (1) is described. Direct, early-stage guanidinylation enabled rapid, convergent access to an immediate clavatadine A precursor. Concomitant lactone hydrolysis and guanidine deprotection with aqueous acid cleanly provided clavatadine A (1) in only four steps (longest linear sequence, 41-43% overall yield).
High-throughput screening in natural product drug discovery in Australia utilising Australia's biodiversity
Publisher: Wiley
Date: 03-1999
DOI: 10.1002/(SICI)1098-2299(199903/04)46:3/4<250::AID-DDR9>3.0.CO;2-8
Pyrazolo[3,4-d]pyrimidine analogues of isoguanine
Publisher: Elsevier BV
Date: 11-1991
Pseudoceratinazole A: a novel bromotyrosine alkaloid from the Australian sponge Pseudoceratina sp.
Publisher: Elsevier BV
Date: 09-2010
Corymbones A and B, Phloroglucinols with Thyrotropin Releasing Hormone Receptor 2 Binding Affinity from the Flowers of Corymbia peltata
Publisher: American Chemical Society (ACS)
Date: 16-04-2008
DOI: 10.1021/NP0706567
Abstract: High-throughput screeing of a plant and marine invertebrate extract library to find natural products with rat thytotropin releasing hormone receptor 2 binding affinity led to the isolation of two new active acylphloroglucinols, corymbones A and B (1 and 2) from flowers of the Queensland tree Corymbia peltata. Their structures were assigned from interpretation of 2D NMR and high-resolution ESIMS data. Compounds 1 and 2 showed rat TRH receptor 2 binding affinity with IC 50 values of 23 and 19 microM, respectively.
Development of a target identification approach using native mass spectrometry
Publisher: Springer Science and Business Media LLC
Date: 27-01-2021
DOI: 10.1038/S41598-021-81859-4
Abstract: A key step in the development of new pharmaceutical drugs is the identification of the molecular target and distinguishing this from all other gene products that respond indirectly to the drug. Target identification remains a crucial process and a current bottleneck for advancing hits through the discovery pipeline. Here we report a method, that takes advantage of the specific detection of protein–ligand complexes by native mass spectrometry (MS) to probe the protein partner of a ligand in an untargeted method. The key advantage is that it uses unmodified small molecules for binding and, thereby, it does not require labelled ligands and is not limited by the chemistry required to tag the molecule. We demonstrate the use of native MS to identify known ligand–protein interactions in a protein mixture under various experimental conditions. A protein–ligand complex was successfully detected between parthenolide and thioredoxin ( Pf Trx) in a five-protein mixture, as well as when parthenolide was mixed in a bacterial cell lysate spiked with Pf Trx. We provide preliminary data that native MS could be used to identify binding targets for any small molecule.
The Relationship between Fenestrations, Sieve Plates and Rafts in Liver Sinusoidal Endothelial Cells
Publisher: Public Library of Science (PLoS)
Date: 24-09-2012
Natural product-based PROteolysis TArgeting Chimeras (PROTACs)
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2NP00038E
Abstract: Natural products exert their action by direct interaction with specific protein targets. Thus, they provide valuable starting points for the design of novel PROTAC molecules, as they present biologically pre-validated protein–ligand pairs.
Solving the Supply of Resveratrol Tetramers from Papua New Guinean Rainforest Anisoptera Species That Inhibit Bacterial Type III Secretion Systems
Publisher: American Chemical Society (ACS)
Date: 18-11-2014
DOI: 10.1021/NP500433Z
Abstract: The supply of (-)-hopeaphenol (1) was achieved via enzymatic biotransformation in order to provide material for preclinical investigation. High-throughput screening of a prefractionated natural product library aimed to identify compounds that inhibit the bacterial virulence type III secretion system (T3SS) identified several fractions derived from two Papua New Guinean Anisoptera species, showing activity against Yersinia pseudotuberculosis outer proteins E and H (YopE and YopH). Bioassay-directed isolation from the leaves of A. thurifera, and similarly A. polyandra, resulted in three known resveratrol tetramers, (-)-hopeaphenol (1), vatalbinoside A (2), and vaticanol B (3). Compounds 1-3 displayed IC50 values of 8.8, 12.5, and 9.9 μM in a luminescent reporter-gene assay (YopE) and IC50 values of 2.9, 4.5, and 3.3 μM in an enzyme-based YopH assay, respectively, which suggested that they could potentially act against the T3SS in Yersinia. The structures of 1-3 were confirmed through a combination of spectrometric, chemical methods, and single-crystal X-ray structure determinations of the natural product 1 and the permethyl ether analogue of 3. The enzymatic hydrolysis of the β-glycoside 2 to the aglycone 1 was achieved through biotransformation using the endogenous leaf enzymes. This significantly enhanced the yield of the target bioactive natural product from 0.08% to 1.3% and facilitates ADMET studies of (-)-hopeaphenol (1).
Grandisine A and B, Novel Indolizidine Alkaloids with Human δ-Opioid Receptor Binding Affinity from the Leaves of the Australian Rainforest Tree Elaeocarpus grandis
Publisher: American Chemical Society (ACS)
Date: 04-02-2005
DOI: 10.1021/JO048525N
Abstract: Two novel indolizidine alkaloids, grandisine A (1) and B (2), and the known alkaloid (-) isoelaeocarpiline (3) were isolated from the leaves of Elaeocarpus grandis and their structures determined by 1D and 2D NMR spectroscopy. The compounds showed affinity for the human delta-opioid receptor. Grandisine A contains a unique tetracyclic skeleton, while grandisine B possesses the unique combination of isoquinuclidinone and indolizidine groups in one molecule.
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