ORCID Profile
0000-0003-4868-845X
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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)
Biological And Medical Chemistry | Medicinal and Biomolecular Chemistry | Organic Chemical Synthesis | Organic Chemistry | Characterisation Of Macromolecules | Electrochemistry | Basic Pharmacology | Analytical Spectrometry | Physical Chemistry (Incl. Structural) | Medical Virology | Nanotechnology | Free Radical Chemistry | Chemical Spectroscopy | Biochemistry and Cell Biology | Organic Chemical Synthesis | Microbiology | Nanochemistry and Supramolecular Chemistry | Physical Chemistry Of Macromolecules | Mechanisms Of Reactions | Physical Organic Chemistry | Biochemistry and Cell Biology not elsewhere classified | Structural Biology (incl. Macromolecular Modelling) | Biophysics | Biological Sciences Not Elsewhere Classified | Industrial Chemistry | Virology | Characterisation of Biological Macromolecules | Ecological Applications | Biomaterials | Global Change Biology | Enzymes | Theoretical And Computational Chemistry Not Elsewhere Classified | Ecological Impacts of Climate Change | Diagnostic Applications |
ANZSRC Socio-Economic Objective (SEO)
Chemical sciences | Treatments (e.g. chemicals, antibiotics) | Infectious diseases | Biological sciences | Prevention—biologicals (e.g. vaccines) | Solar-photoelectric | Aboriginal and Torres Strait Islander health | Physical sciences | Organs, diseases and abnormal conditions not elsewhere classified | Global climate change adaptation measures | Occupational Health | Effects of Climate Change and Variability on Antarctic and Sub-Antarctic Environments (excl. Social Impacts) | Ecosystem Adaptation to Climate Change | Ecosystem Assessment and Management of Antarctic and Sub-Antarctic Environments | Energy storage | Higher education | Medical instrumentation | Cancer and related disorders | Other | Paints | Human Pharmaceutical Treatments (e.g. Antibiotics) | Expanding Knowledge in the Chemical Sciences | Expanding Knowledge in the Biological Sciences
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Publications
Phytochemical Studies on Two Australian Anigozanthos Plant Species
Publisher: American Chemical Society (ACS)
Date: 06-07-2017
DOI: 10.1021/ACS.JNATPROD.7B00063
Abstract: Phytochemical studies of two Australian Anigozanthos (kangaroo paw) species, A. rufus and A. pulcherrimus, resulted in the identification of 13 secondary metabolites. 2-Amino-6-O-p-coumarylheptanedioic acid (3) and chalcone-5'-O-(4-O-p-coumaryl)-O-β-d-glucopyranoside (12) are reported as new compounds and are accompanied by nine flavonoids (2, 5-11, 13) and two anthocyanins (1, 4). Compounds 1 and 4 were isolated as red solids from A. rufus and are likely responsible for the coloration of the flowers. Compounds 1, 3, and 6 showed weak antimicrobial activities against Acinetobacter baumannii ATCC 19606 at concentrations of 52.4, 94.9, and 53.9 μM, respectively.
A structure-based design approach to advance the allyltyrosine-based series of HIV integrase inhibitors
Publisher: Elsevier BV
Date: 03-2018
Cationic biaryl 1,2,3-triazolyl peptidomimetic amphiphiles targeting Clostridioides (Clostridium) difficile: Synthesis, antibacterial evaluation and an in vivo C. difficile infection model
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.EJMECH.2019.02.068
Abstract: Clostridioides (formerly Clostridium) difficile is a Gram-positive anaerobic bacterial pathogen that causes severe gastrointestinal infection in humans. The current chemotherapeutic options are vastly inadequate, expensive and limited this results in an exorbitant medical and financial burden. New, inexpensive chemotherapeutic treatments for C. difficile infection with improved efficacy are urgently needed. A streamlined synthetic pathway was developed to allow access to 38 novel mono- and di-cationic biaryl 1,2,3-triazolyl peptidomimetics with increased synthetic efficiency, aqueous solubility and enhanced antibacterial efficacy. The monocationic arginine derivative 28 was identified as a potent, Gram-positive selective antibacterial with MIC values of 4 μg/mL against methicillin-resistant Staphylococcus aureus and 8 μg/mL against C. difficile. Furthermore, the dicationic bis-triazole analogue 50 was found to exhibit broad-spectrum activity with substantial Gram-negative efficacy against Acinetobacter baumannii (8 μg/mL), Pseudomonas aeruginosa (8 μg/mL) and Klebsiella pneumoniae (16 μg/mL) additionally, compound 50 displayed reduced haemolytic activity (<13%) in an in vitro haemolysis assay. Membrane-disruption assays were conducted on selected derivatives to confirm the membrane-active mechanism of action inherent to the synthesized hiphilic compounds. A comparative solubility assay was developed and utilized to optimize the aqueous solubility of the compounds for in vivo studies. The biaryl peptidomimetics 28 and 67 were found to exhibit significant efficacy in an in vivo murine model of C. difficile infection by reducing the severity and slowing the onset of disease.
Inhibition of TNF-α production in LPS-activated THP-1 monocytic cells by the crude extracts of seven Bhutanese medicinal plants
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.JEP.2013.05.055
Abstract: Seven studied medicinal plants Aconitum laciniatum, Ajania nubigena, Codonopsis bhutanica, Corydalis crispa, Corydalis dubia, Meconopsis simplicifolia and Pleurospermum amabile, are currently used in the Bhutanese Traditional Medicine (BTM) for the management of different types of disorders including the diseases that bore relevance to various inflammatory conditions. This study aimed to evaluate the inhibition of TNF-α production in LPS-activated THP-1 monocytic cells by the crude extracts of seven selected Bhutanese medicinal plants. It is expected to (a) generate a scientific basis for their use in the BTM and (b) form a basis for prioritization of the seven plants for further phytochemical and anti-inflammatory studies. Seven plants were selected using an ethno-directed bio-rational approach and their crude extracts were prepared using four different solvents (methanol, hexane, dichloromethane and chloroform). The TNF-α inhibitory activity of these extracts was determined by cytokine-specific sandwich quantitative enzyme-linked immunosorbent assays (ELISAs). The results were quantified statistically and the statistical significance were evaluated by GraphPad Prism version 5.01 using Student's t-test with one-tailed distribution. A p-value ≤0.05 was considered statistically significant. Of the seven plants studied, the crude extracts of six of them inhibited the production of pro-inflammatory cytokine, TNF-α in LPS-activated THP-1 monocytic cells. Amongst the six plants, Corydalis crispa gave the best inhibitory activity followed by Pleurospermum amabile, Ajania nubigena, Corydalis dubia, Meconopsis simplicifolia and Codonopsis bhutanica. Of the 13 extracts that exhibited statistically significant TNF-α inhibitory activity (p<0.05 p<0.01), five of them showed very strong inhibition when compared to the DMSO control and RPMI media. Six medicinal plants studied here showed promising TNF-α inhibitory activity. These findings rationalize the traditional use of these selected medicinal plants in the BTM as an in idual plant or in combination with other ingredients for the treatment of disorders bearing relevance to the inflammatory conditions. The results forms a good preliminary basis for the prioritization of candidate plant species for an in-depth phytochemical study and anti-inflammatory activity screening of the pure compounds contained within those seven plants.
The medicinal chemistry of dengue fever
Publisher: American Chemical Society (ACS)
Date: 09-09-2009
DOI: 10.1021/JM900652E
Chikungunya Virus: Emerging Targets and New Opportunities for Medicinal Chemistry
Publisher: American Chemical Society (ACS)
Date: 23-10-2013
DOI: 10.1021/JM400460D
Abstract: Chikungunya virus is an emerging arbovirus that is widespread in tropical regions and is spreading quickly to temperate climates with recent epidemics in Africa and Asia and documented outbreaks in Europe and the Americas. It is having an increasingly major impact on humankind, with potentially life-threatening and debilitating arthritis. There is no treatment available, and only in the past 24 months have lead compounds for development as potential therapeutics been reported. This Perspective discusses the chikungunya virus as a significant, new emerging topic for medicinal chemistry, highlighting the key viral target proteins and their molecular functions that can be used in drug design, as well as the most important ongoing developments for anti-chikungunya virus research. It represents a complete picture of the current medicinal chemistry of chikungunya, supporting the development of chemotherapeutics through drug discovery and design targeting this virus.
Identification of chikungunya virus nsP2 protease inhibitors using structure-base approaches
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.JMGM.2015.01.001
Abstract: The nsP2 protease of chikungunya virus (CHIKV) is one of the essential components of viral replication and it plays a crucial role in the cleavage of polyprotein precursors for the viral replication process. Therefore, it is gaining attention as a potential drug design target against CHIKV. Based on the recently determined crystal structure of the nsP2 protease of CHIKV, this study identified potential inhibitors of the virus using structure-based approaches with a combination of molecular docking, virtual screening and molecular dynamics (MD) simulations. The top hit compounds from database searching, using the NCI Diversity Set II, with targeting at five potential binding sites of the nsP2 protease, were identified by blind dockings and focused dockings. These complexes were then subjected to MD simulations to investigate the stability and flexibility of the complexes and to gain a more detailed insight into the interactions between the compounds and the enzyme. The hydrogen bonds and hydrophobic contacts were characterized for the complexes. Through structural alignment, the catalytic residues Cys1013 and His1083 were identified in the N-terminal region of the nsP2 protease. The absolute binding free energies were estimated by the linear interaction energy approach and compared with the binding affinities predicted with docking. The results provide valuable information for the development of inhibitors for CHIKV.
Positional Isomers of Biphenyl Antimicrobial Peptidomimetic Amphiphiles
Publisher: American Chemical Society (ACS)
Date: 03-02-2021
Reactions of iminoglycines with C60 fullerene and their unambiguous characterisation using NMR spectroscopy
Publisher: Elsevier BV
Date: 07-2006
Photoprotection enhanced by red cell wall pigments in three East Antarctic mosses
Publisher: Springer Science and Business Media LLC
Date: 21-11-2018
2,7-Dimethylthiazolo[4,5-d]pyradazine-4-(5H)-thione: A Corticotrophin-Releasing Hormone Type 1 Receptor Agonist
Publisher: CSIRO Publishing
Date: 2000
DOI: 10.1071/CH99015
Abstract: Thiazoles, including 2,7-dimethylthiazolo[4,5-d]pyradazine-4-(5H)-thione (4b) and the corresponding 5-phenylthiazolo[4,5-d]pyradazine-4-methylthiol (5a), were synthesized as part of an ongoing investigation into corticotrophin-releasing hormone (CRH) type 1 receptor activity. Subsequent screening indicated the successful discovery of receptor agonists. Assay results indicated a 52 and 3% increase in β-endorphin release after the administration of 100 M (4b) and (5a), respectively. It is believed that this represents the first evidence of this class of compounds displaying CRH type 1 receptor agonist activity.
Chapter 2 - Ring Synthesis
Publisher: Elsevier
Date: 2013
Fullerene Van der Waals Oligomers as Electron Traps
Publisher: American Chemical Society (ACS)
Date: 24-07-2014
DOI: 10.1021/JA505949M
Abstract: Density functional theory calculations indicate that van der Waals fullerene dimers and larger oligomers can form interstitial electron traps in which the electrons are even more strongly bound than in isolated fullerene radical anions. The fullerenes behave like "super atoms", and the interstitial electron traps represent one-electron intermolecular σ-bonds. Spectroelectrochemical measurements on a bis-fullerene-substituted peptide provide experimental support. The proposed deep electron traps are relevant for all organic electronics applications in which non-covalently linked fullerenes in van der Waals contact with one another serve as n-type semiconductors.
Stimuli-Responsive Cycloaurated OFF-ON Switchable Anion Transporters
Publisher: Wiley
Date: 11-08-2020
Abstract: Anion transporters have shown potential application as anti‐cancer agents that function by disrupting homeostasis and triggering cell death. In this research article we report switchable anion transport by gold complexes of anion transporters that are “switched on” in situ in the presence of the reducing agent GSH by decomplexation of gold. GSH is found in higher concentrations in tumors than in healthy tissue and hence this approach offers a strategy to target these systems to tumors.
Phytochemical and Pharmacological Studies on Four Indonesian Epiphytic Medicinal Plants: Drynaria rigidula, Hydnophytum formicarum, Usnea misaminensis, and Calymperes schmidtii
Publisher: SAGE Publications
Date: 06-2019
Binaphthyl-anchored antibacterial tripeptide derivatives with hydrophobic C-terminal amino acid variations
Publisher: Beilstein Institut
Date: 09-08-2012
DOI: 10.3762/BJOC.8.142
Abstract: The facile synthesis of seven new dicationic tripeptide benzyl ester derivatives, with hydrophobic group variations in the C-terminal amino acid component, is described. Moderate to good activity was seen against Gram-positive bacteria in vitro. One cyclohexyl-substituted compound 2c was tested more widely and showed good potency (MIC values ranging from 2–4 μg/mL) against antibiotic-resistant strains of Staphylococcus aureus and Enterococci (VRE, VSE), and against Staphylococcus epidermidis .
Control of Hepatitis C: A Medicinal Chemistry Perspective
Publisher: American Chemical Society (ACS)
Date: 09-12-2005
DOI: 10.1021/JM0400101
How To Make Nitroaromatic Compounds Glow: Next‐Generation Large X‐Shaped, Centrosymmetric Diketopyrrolopyrroles
Publisher: Wiley
Date: 10-07-2020
Predicting phosphirane air stability using density functional theory
Publisher: Wiley
Date: 16-07-2020
DOI: 10.1002/POC.4110
Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo
Publisher: Beilstein Institut
Date: 15-04-2015
DOI: 10.3762/BJOC.11.54
Abstract: Diversity-directed synthesis based on the cascade allylation chemistry of indigo, with its embedded 2,2’-diindolic core, has resulted in rapid access to new ex les of the hydroxy-8a,13-dihydroazepino[1,2- a :3,4- b ']diindol-14(8 H )-one skeleton in up to 51% yield. Additionally a derivative of the novel bridged heterocycle 7,8-dihydro-6 H -6,8a-epoxyazepino[1,2- a :3,4- b ']diindol-14(13 H )-one was produced when the olefin of the allylic substrate was terminally disubstituted. Further optimisation also produced viable one-pot syntheses of derivatives of the spiro(indoline-2,9'-pyrido[1,2- a ]indol)-3-one (65%) and pyrido[1,2,3- s , t ]indolo[1,2- a ]azepino[3,4- b ]indol-17-one (72%) heterocyclic systems. Ring-closing metathesis of the N , O -diallylic spiro structure and subsequent Claisen rearrangement gave rise to the new (1 R ,8a S ,17a S )-rel-1,2-dihydro-1-vinyl-8 H ,17H,9 H -benz[2',3']pyrrolizino[1',7 a ':2,3]pyrido[1,2- a ]indole-8,17-(2 H ,9 H )-dione heterocyclic system.
The attempted stereoselective synthesis of chiral 2,2′-biindoline
Publisher: Elsevier BV
Date: 08-2010
Synthesis and antibacterial activity of some binaphthyl-supported macrocycles containing a cationic amino acid
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.BMC.2011.04.013
Abstract: As part of a programme investigating antibacterial cyclic macrocycles containing a cationic amino acid with an internal aromatic hydrophobic scaffold, we previously reported a macrocycle anchored at the 3,3'-positions of a 1,1'-binaphthyl unit. This was prepared via key intermediates containing an internal allylglycine and an allyl-substituted binaphthyl unit for a subsequent ring-closing metathesis reaction. This paper presents some structure-activity relationship studies with additional macrocycles based on this lead compound against Staphylococcus aureus together with the antibacterial activity of two related acyclic compounds.
Convergent total synthesis of the michellamines
Publisher: Elsevier BV
Date: 10-1994
Cascade reactions of indigo with oxiranes and aziridines: efficient access to dihydropyrazinodiindoles and spiro-oxazocinodiindoles
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8OB00865E
Abstract: Cascade reactions of indigo with strained electrophiles affords access to previously unknown oxazocino, pyrazino, and diazepino diindoles with selective anti-plasmodial activity.
Efficient synthesis and antioxidant activity of coelenterazine analogues
Publisher: Elsevier BV
Date: 11-2014
Synthesis of some cyclic indolic peptoids as potential antibacterials
Publisher: Elsevier BV
Date: 10-2006
Molecular Docking Studies to Explore Potential Binding Pockets and Inhibitors for Chikungunya Virus Envelope Glycoproteins
Publisher: Springer Science and Business Media LLC
Date: 11-03-2018
DOI: 10.1007/S12539-016-0209-0
Abstract: The chikungunya virus (CHIKV) envelope glycoproteins are considered important potential targets for anti-CHIKV drug discovery due to their crucial roles in virus attachment and virus entry. In this study, using two available crystal structures of the immature and mature forms of envelope glycoproteins, virtual screenings based on blind dockings and focused dockings were carried out to identify potential binding pockets and hit compounds for the virus. The chemical library database of compounds, NCI Diversity Set II, was used in these docking studies. In addition to reproducing previously reported ex les, new binding pockets were identified, e.g., Pocket 2 in the 3N40, and Pocket 2 and Pocket 3 in the 3N42. Convergences in conformational s ling in docking using AutoDock Vina were evaluated. An analysis of docking results was carried out to understand interactions of the envelope glycoproteins complexes. Some key residues for interactions, for ex le Gly91 and His230, are identified as possessing important roles in the fusion process.
Evaluation of an ethnopharmacologically selected Bhutanese medicinal plants for their major classes of Phytochemicals and biological activities
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.JEP.2011.06.032
Abstract: As many as 229 medicinal plants have been currently used in the Bhutanese Traditional Medicine (BTM) as a chief ingredient of polyherbal formulations and these plants have been in idually indicated for treating various types of infections including malaria, tumor, and microbial. We have focused our study only on seven species of these plants. We aim to evaluate the antiplasmodial, antimicrobial, anti-Trypanosoma brucei rhodesiense and cytotoxicity activities of the seven medicinal plants of Bhutan selected using an ethno-directed bio-rational approach. This study creates a scientific basis for their use in the BTM and gives foundation for further phytochemical and biological evaluations which can result in the discovery of new drug lead compounds. A three stage process was conducted which consisted of: (1) an assessment of a pharmacopoeia and a formulary book of the BTM for their mode of plant uses (2) selecting 25 anti-infective medicinal plants based on the five established criteria, collecting them, and screening for their major classes of phytochemicals using appropriate test protocols and (3) finally analyzing the crude extracts of the seven medicinal plants, using the standard test protocols, for their antiplasmodial, antimicrobial, anti-Trypanosoma brucei rhodesiense and cytotoxicity activities as directed by the ethnopharmacological uses of each plant. Out of 25 medicinal plants screened for their major classes of phytochemicals, the majority contained tannins, alkaloids and flavonoids. Out of the seven plant species investigated for their biological activities, all seven of them exhibited mild antimicrobial properties, five plants gave significant in vitro antiplasmodial activities, two plants gave moderate anti-Trypanosoma brucei rhodesiense activity, and one plant showed mild cytotoxicity. Meconopsis simplicifolia showed the highest antiplasmodial activity with IC(50) values of 0.40 μg/ml against TM4/8.2 strain (a wild type chloroquine and antifolate sensitive strain) and 6.39 μg/ml against K1CB1 (multidrug resistant strain) strain. Significantly the extracts from this plant did not show any cytotoxicity. These findings provide the scientific basis for the use of seven medicinal plants in the BTM for the treatment of malaria, microbial infections, infectious fevers, and the Trypanosoma brucei rhodesiense infection. The results also form a good preliminary basis for the prioritization of candidate plant species for further in-depth phytochemical and pharmacological investigations toward our quest to unearth lead antiparasitic, anticancer and antimicrobial compounds.
Vascular Epiphytic Medicinal Plants as Sources of Therapeutic Agents: Their Ethnopharmacological Uses, Chemical Composition, and Biological Activities
Publisher: MDPI AG
Date: 24-01-2020
DOI: 10.3390/BIOM10020181
Abstract: This is an extensive review on epiphytic plants that have been used traditionally as medicines. It provides information on 185 epiphytes and their traditional medicinal uses, regions where Indigenous people use the plants, parts of the plants used as medicines and their preparation, and their reported phytochemical properties and pharmacological properties aligned with their traditional uses. These epiphytic medicinal plants are able to produce a range of secondary metabolites, including alkaloids, and a total of 842 phytochemicals have been identified to date. As many as 71 epiphytic medicinal plants were studied for their biological activities, showing promising pharmacological activities, including as anti-inflammatory, antimicrobial, and anticancer agents. There are several species that were not investigated for their activities and are worthy of exploration. These epipythes have the potential to furnish drug lead compounds, especially for treating cancers, and thus warrant indepth investigations.
Antimalarial alkaloids from a Bhutanese traditional medicinal plant Corydalis dubia
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.JEP.2012.06.037
Abstract: Corydalis dubia is used in Bhutanese traditional medicine as a febrifuge and for treating infections in the blood, liver and bile which correlate to the signs and symptoms of malarial and microbial infections. To validate the ethnopharmacological uses of the plant and to discover potential new therapeutic drug leads. C. dubia was collected from Bhutan and the alkaloids were obtained using acid-base fractionation and separation by repeated column and preparative plate chromatography. The alkaloids were identified from analysis of their physiochemical and spectroscopic data and were tested for antiplasmodial, antimicrobial and cytotoxicity activities. A systematic extraction and isolation protocol yielded one new natural product, dubiamine, and seven known isoquinoline alkaloids, scoulerine, cheilanthifoline, protopine, capnoidine, bicuculline, corydecumbine and hydrastine. Among the four alkaloids tested, scoulerine showed the best antiplasmodial activity with IC(50) values of 5.4μM and 3.1μM against the antifolate sensitive and the multidrug resistant P. falciparum strains: TM4/8.2 and K1CB1, respectively. None of the alkaloids tested showed significant antimicrobial or cytotoxicity activities. The antiplasmodial test results, of the isolated alkaloid components, are commensurated with the ethnopharmacological uses of this plant.
A Photoreactor-Interfaced Mass Spectrometer: An Online Platform to Monitor Photochemical Reactions
Publisher: American Chemical Society (ACS)
Date: 13-10-2023
Ring-opening and -expansion of 2,2′-biaziridine: Access to diverse enantiopure linear and bicyclic vicinal diamines
Publisher: American Chemical Society (ACS)
Date: 07-08-2014
DOI: 10.1021/OL502164B
Abstract: The chiral pool-derived 1,1'-ditosyl-2,2'-biaziridine has been established as a valuable building block for the ergent synthesis of enantiopure vicinal diamines. Efficient procedures for the regioselective ring opening of the biaziridine with oxygen, sulfur, nitrogen, and carbon nucleophiles are described. The strategic use of nucleophiles bearing pendant functionality allows further elaboration of the acyclic products to a variety of 2,2'-bicyclic-embedded diamines. Desymmetrization of the biaziridine has also been accomplished via the selective monoaddition of organocuprates.
Perylene-Monoimides: Singlet Fission Down-Conversion Competes with Up-Conversion by Geminate Triplet–Triplet Recombination
Publisher: American Chemical Society (ACS)
Date: 22-06-2020
Regioselective convergent synthesis of 2-arylidene thiazolo[3,2-a]pyrimidines as potential anti-chikungunya agents
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0RA00257G
Abstract: Convergent and convenient regioselective synthesis of novel thiazolo[2,3- a ]pyrimidines was accomplished using the one-pot reaction of 6-ethylthiouracil, bromoacetic acid, anhydrous sodium acetate, acetic anhydride, acetic acid and suitable aldehyde.
Arsenous chloride-free synthesis of cyclic tertiary organoarsines from arylarsine oxides and di-Grignard reagents
Publisher: Elsevier BV
Date: 06-2015
The first syntheses of enantiopure 2,2′-biindoline
Publisher: Royal Society of Chemistry (RSC)
Date: 2010
DOI: 10.1039/C0CC04045B
Abstract: The first two syntheses of chiral 2,2'-biindoline are reported either in five steps from 2,2'-bioxirane, or three steps from 2,2'-biaziridine, both with exceptional enantiopurity.
Effects of methamphetamine and its primary human metabolite, p-hydroxymethamphetamine, on the development of the Australian blowfly Calliphora stygia
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.FORSCIINT.2014.05.003
Abstract: The larvae of necrophagous fly species are used as forensic tools for the determination of the minimum postmortem interval (PMI). However, any ingested drugs in corpses may affect larval development, thus leading to incorrect estimates of the period of infestation. This study investigated the effects of meth hetamine and its metabolite, p-hydroxymeth hetamine, on the forensically important Australian blowfly Calliphora stygia. It was found that the presence of the drugs significantly accelerated larval growth and increased the size of all life stages. Furthermore, drug-exposed s les remained as pupae for up to 78 h longer than controls. These findings suggest that estimates of the minimum PMI of meth hetamine-dosed corpses could be incorrect if the altered growth of C. stygia is not considered. Different temperatures, drug concentrations and substrate types are also likely to affect the development of this blowfly. Pending further research, the application of C. stygia to the entomological analysis of meth hetamine-related fatalities should be appropriately qualified.
New cyclic peptides via ring-closing metathesis reactions and their anti-bacterial activities
Publisher: Elsevier BV
Date: 12-2008
Synthesis, molecular modeling and biological activity of methyl and thiomethyl substituted pyrimidines as corticotropin releasing hormone type 1 antagonists
Publisher: Royal Society of Chemistry (RSC)
Date: 2003
DOI: 10.1039/B305458F
Abstract: Four small, targeted libraries of differentially substituted amino pyrimidines were synthesized in moderate to good yields. Excellent regiochemistry was observed for substitution at C2/C4 with selectivity > 50:1 noted. All analogues were screened for their ability to interact with CRH1 and CRH2 receptors. In all instances only poor agonistic and/or antagonistic behaviour was noted at CRH2. However, several compounds were potent and selective CRH1 antagonists, most notably 13a Ki = 39 nM. Additionally we have utilized these data and that recently reported by others to refine our original CRH1 pharmacophore (J Med. Chem., 1999, 42, 2351-2357).
Structural Reassignment of the Mono- and Bis-Addition Products from the Addition Reactions of N-(Diphenylmethylene)glycinate Esters to [60]Fullerene under Bingel Conditions
Publisher: American Chemical Society (ACS)
Date: 16-09-2005
DOI: 10.1021/JO051282U
Abstract: The addition of N-(diphenylmethylene)glycinate esters (Ph2C=NCH2CO2R) to [60]fullerene under Bingel conditions gives [60]fullerenyldihydropyrroles and not methano[60]fullerenyl iminoesters [C60C(CO2R)(N=CPh2)] as previously reported. Unequivocal evidence for the structure of C60C(CO2Et)(N=CPh2) was provided by INADEQUATE NMR studies on 13C enriched material. New mechanistic details are proposed to account for the formation of [60]fullerenyldihydropyrroles and their reductive ring-opening reactions.
Aryl Nitro Reduction with Iron Powder or Stannous Chloride under Ultrasonic Irradiation
Publisher: Informa UK Limited
Date: 08-2007
Anti-cancer Evaluation of Depsides Isolated from Indonesian Folious Lichens: Physcia millegrana, Parmelia dilatata and Parmelia aurulenta
Publisher: MDPI AG
Date: 08-10-2020
DOI: 10.3390/BIOM10101420
Abstract: Cancer is a serious health burden on global societies. The discovery and development of new anti-cancer therapies remains a challenging objective. Although it has been shown that lichen secondary metabolites may be potent sources for new anti-cancer agents, the Indonesian- grown folious lichens, Physcia millegrana, Parmelia dilatata and Parmeila aurulenta, have not yet been explored. In this study exhaustive preparative high-performance liquid chromatography was employed to isolate the lichen constituents with spectroscopic and spectrometric protocols identifying nine depsides 9–17, including the new methyl 4-formyl-2,3-dihydroxy-6-methylbenzoate 13. The cytotoxicity of the depsides towards cancer cells was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results indicated lowest toxicity of the depsides towards human A549 lung cancer cells. Importantly, the di-depsides (11, 12 and 17) showed greatest toxicity, indicating that these structures are biologically more active than the mono-depsides against the HepG2 liver cancer, A549 lung cancer and HL-60 leukemia cell lines.
Synthesis and antibacterial studies of binaphthyl-based tripeptoids. Part 1
Publisher: Elsevier BV
Date: 04-2010
DOI: 10.1016/J.BMC.2010.02.033
Abstract: An efficient synthesis of 29 new binaphthyl-based neutral, and mono- and di-cationic, peptoids is described. Some of these compounds had antibacterial activities with MIC values of 1.9-3.9microg/mL against Staphylococcus aureus. One peptoid had a MIC value of 6microg/mL against a methicillin-resistant strain of S. aureus (MRSA) and a MIC value of 2microg/mL against vancomycin-resistant strains of enterococci (VRE).
A Mild and General Method for the Synthesis of 5-Substituted and 5,5-Disubstituted Fulleroprolines
Publisher: American Chemical Society (ACS)
Date: 21-02-2008
DOI: 10.1021/OL8002157
Abstract: The reductive ring-opening of fullerenyldihydropyrrole yields ethyl N-benzhydryl fullerenyl[60]glycinate, which is deprotected to give ethyl fullerenylglycinate. The free amine is able to react with a variety of aldehydes and ketones in a Mannich-type process to produce 5-substituted and 5,5-disubstituted fulleroprolines and represents a versatile and general strategy to this class of compounds.
Cationic biaryl 1,2,3-triazolyl peptidomimetic amphiphiles: synthesis, antibacterial evaluation and preliminary mechanism of action studies
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.EJMECH.2019.02.013
Abstract: Synthetic small molecular antimicrobial peptidomimetics represent a promising new class of potential antibiotics due to their membrane-disrupting ability and their decreased propensity for bacterial resistance. A library of 43 mono- and di-cationic biaryl 1,2,3-triazolyl peptidomimetics was designed and synthesized based upon previously established lead biarylpeptidomimetics and a known pharmacophore. A reliable, facile and modular synthetic pathway allowed for the efficient synthesis of multiple unique scaffolds which were subjected to ergent derivatization to furnish the hiphilic compounds. In vitro testing revealed enhanced antibacterial efficacy against a range of pathogenic bacteria, including bacterial isolates with methicillin, vancomycin, daptomycin, or multi-drug resistance. Preliminary time-kill kinetics and membrane-disruption assays revealed a likely membrane-active mechanism for the tested peptidomimetics. An optimal balance between hydrophobicity and cationic charge was found to be essential for reduced cytotoxicity/haemolysis (i.e. membrane selectivity) and enhanced Gram-negative activity. The cationic biaryl hiphile 81 was identified as a potent, broad-spectrum peptidomimetic with activity against Gram-positive (methicillin-resistant Staphylococcus aureus - MIC = 2 μg/mL) and Gram-negative (Escherichia coli - MIC = 4 μg/mL) pathogenic bacteria.
Binaphthyl scaffolded peptoids via ring-closing metathesis reactions and their anti-bacterial activities
Publisher: Elsevier BV
Date: 06-2009
DOI: 10.1016/J.BMCL.2009.04.046
Abstract: An efficient synthesis of four new acyclic and four new cyclic binaphthyl-based cationic peptoids is described. These compounds had anti-bacterial activities with MIC values of 4-62 microg/mL against Staphylococcus aureus.
Binaphthyl-Based Dicationic Peptoids with Therapeutic Potential
Publisher: Wiley
Date: 11-12-2009
A potent fluorescent transmembrane HCl transporter perturbs cellular pH and promotes cancer cell death
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D3OB00128H
Abstract: A series of fluorescent coumarin-based bis-ureas have been synthesised. These compounds show strong HCl cotransport properties in model vesicle systems. Cellular localisation studies show that cytotoxic compound 4 localises in lysosomes and perturbs cellular pH.
Stimuli‐Responsive Cycloaurated “OFF‐ON” Switchable Anion Transporters
Publisher: Wiley
Date: 11-08-2020
Abstract: Anion transporters have shown potential application as anti‐cancer agents that function by disrupting homeostasis and triggering cell death. In this research article we report switchable anion transport by gold complexes of anion transporters that are “switched on” in situ in the presence of the reducing agent GSH by decomplexation of gold. GSH is found in higher concentrations in tumors than in healthy tissue and hence this approach offers a strategy to target these systems to tumors.
Alkaloids from the root of Indonesian Annona muricata L
Publisher: Informa UK Limited
Date: 08-07-2019
Investigation of thiazolyl–benzothiophenamides as potential agents for African sleeping sickness
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0MD00277A
Abstract: African sleeping sickness is a potentially fatal neglected disease affecting sub-Saharan Africa.
Cyclic Phosphine Oxides and Phosphinamides from Di-Grignard Reagents and Phosphonic Dichlorides: Modular Access to Annulated Phospholanes
Publisher: American Chemical Society (ACS)
Date: 23-09-2015
Abstract: The reaction between 1,4-di-Grignard reagents and phosphonous(III) dichlorides is a classical method for the direct synthesis of phospholanes. Reported here is an extension of this approach to the preparation of value-added, annulated phospholane oxides, achieved through the combination of carbocyclic-fused di-Grignard reagents and readily available phosphonic(V) dichlorides. The procedure is amenable to (benz)annulation at both the 2,3- and 3,4-positions of the phospholane ring, and a variety of aliphatic, cyclic and aryl P-electrophiles are tolerated in reasonable to excellent yields.
Binaphthyl-1,2,3-triazole peptidomimetics with activity against Clostridium difficile and other pathogenic bacteria
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5OB00576K
Abstract: Designed binaphthyl-based, cationic peptidomimetic antimicrobials targeting C. difficile , incorporating a click-derived 1,2,3-triazole ester isostere at the C-terminus MICs of 4 μg mL −1 against three human isolates of C. difficile .
Synthesis and Density Functional Theory Studies of Azirinyl and Oxiranyl Functionalized Isoindigo and (3Z,3’Z)-3,3’-(ethane-1,2-diylidene)bis(indolin-2-one) Derivatives
Publisher: MDPI AG
Date: 10-10-2019
DOI: 10.3390/MOLECULES24203649
Abstract: The design and synthesis of functionalized isoindigo compounds by reaction of isoindigo with (S)-glycidyl tosylate, epibromohydrin, 2-(bromomethyl)-1-(arylsulfonyl)aziridine, and 2-(bromomethyl)-1-(alkylsulfonyl)aziridine in the presence of MeONa proceed under mild conditions in moderate yields. (3Z,3’Z)-3,3’-(Ethane-1,2-diylidene)bis(1-(oxiran-2-ylmethyl)indolin-2-one), with an extended central olefin π-conjugated moiety was also reacted with methyl-oxiranes to give the corresponding N,N’-disubstituted derivative. Calculations with DFT and TD-DFT of hypothetical isoindigo-thiophene DA molecules with various electron withdrawing substituents, including aziridine, oxirane, nitrile, carbonyl, and sulfonate, indicated that the proximity and strength of the functional group have a significant effect on the HOMO, LUMO, vertical excitation energy, and oscillator strength of the π–π* transitions.
Isolation of Antimalarial Agents From Indonesian Medicinal Plants: Swietenia mahagoni and Pluchea indica
Publisher: SAGE Publications
Date: 2022
DOI: 10.1177/1934578X211068926
Abstract: Malaria is a neglected tropical disease that still demands serious efforts to tackle successfully, including the need for new antimalarial lead compounds to combat drug-resistant Plasmodium. Intensive phytochemical and pharmacological investigation into the Indonesian medicinal plants Swietenia mahagoni and Pluchea indica successfully revealed 5 constituents. Antimalarial bioassays indicated 34,5-tri- O-caffeoylquinic acid (4) to be the most active against Plasmodium falciparum 3D7 and Dd2 strains with IC 50 values of 8.2 and 8.8 µM, respectively. No cytotoxicity was observed against Human Embryonic Kidney cells at a concentration of 40 µM.
[60] Fullerenyl amino acids and peptides: A review of their synthesis and applications
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4RA07310J
Abstract: This review reports on the latest progress in the synthesis of fullerenyl amino acids and related derivatives, and categorises the molecules into functional types for different uses: these include directly attached fullerenyl amino acids, fullerenyl N- and C-capping amino acids, and those amino acids in which the [60]fullerene group is attached to the amino acid side chain.
The discovery of allyltyrosine based tripeptides as selective inhibitors of the HIV-1 integrase strand-transfer reaction
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6OB00950F
Abstract: From library screening of synthetic antimicrobial peptides, an O -allyltyrosine-based tripeptide HIV-1 integrase (IN) inhibitor was identified. Subsequent optimisation afforded an analogue exhibiting an IC 50 value of 2.5 μM.
Synthesis and antimicrobial activity of binaphthyl-based, functionalized oxazole and thiazole peptidomimetics
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5OB01638J
Abstract: Thirty two new binaphthyl-based, oxazole and thiazole peptidomimetics were prepared, which showed antibacterial activity (MICs 1–16 μg mL −1 ) against both Gram positive and negative isolates.
Reductive ring opening reactions of diphenyldihydrofullerenylpyrroles
Publisher: Elsevier BV
Date: 10-2007
Dengue Virus Therapeutic Intervention Strategies Base on Viral, Vector and Host Factors Involved in Disease Pathogenesis
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.PHARMTHERA.2012.10.007
Abstract: Dengue virus (DV) is the most widespread arbovirus, being endemic in over 100 countries, and is estimated to cause 50 million infections annually. Viral factors, such as the genetic composition of the virus strain can play a role in determining the virus virulence and subsequent clinical disease severity. Virus vector competence plays an integral role in virus transmission and is a critical factor in determining the severity and impact of DV outbreaks. Host genetic variations in immune-related genes, including the human leukocyte antigen, have also been shown to correlate with clinical disease and thus may play a role in regulating disease severity. The host's immune system, however, appears to be the primary factor in DV pathogenesis with the delicate interplay of innate and acquired immunity playing a crucial role. Although current research of DV pathogenesis has been limited by the lack of an appropriate animal model, the development of DV therapeutics has been a primary focus of research groups around the world. In the past decade advances in both the development of vaccines and anti-virals have increased in dramatically. This review summarises the current understanding of viral, vector and host factors which contribute to dengue virus pathogenesis and how this knowledge is critically important in the development of pharmaceutical interventions.
Desymmetrization Reactions of Indigo with Grignard Reagents for the Synthesis of Selective Antiplasmodial [1H,3′H]-3-Aryl-2,2′-diindol-3′-ones
Publisher: American Chemical Society (ACS)
Date: 08-2019
Abstract: The nucleophilic addition of organomagnesium and organolithium species to the cheap and robust natural dye indigo led to desymmetrization of the heterocyclic nucleus via a Grignard addition-dehydration procedure. Twenty-seven ersely functionalized [1
The Prevention of Preterm Labour - Corticotropin Releasing Hormone Type 1 Receptors as a Target for Drug Design and Development
Publisher: Bentham Science Publishers Ltd.
Date: 06-2003
Abstract: The role of the corticotropin releasing hormone in the onset of labour and the subsequent medicinal chemistry implications of CRH antagonists for the prevention of premature birth, and identification of the CRH type 1 receptor as the target for this drug design, are reviewed here.
The evolution of sexually dimorphic cuticular hydrocarbons in blowflies (Diptera: Calliphoridae)
Publisher: Wiley
Date: 10-08-2020
DOI: 10.1111/JEB.13685
Major Transitions in Cuticular Hydrocarbon Expression Coincide with Sexual Maturity in a Blowfly (Diptera: Calliphoridae)
Publisher: Springer Science and Business Media LLC
Date: 07-2020
Synthesis of 7α-Methoxy-7-(4-phenyl-1H-1,2,3-triazol-1-yl)acetamino-3′-arylthio-cephalosporic Acid Derivatives from 7-Aminocephalosporic Acid
Publisher: MDPI AG
Date: 30-10-2023
Enantiopure trans -4,5-disubstituted 2-imidazolidinones via copper(I)-catalyzed ring opening of 1,1′-DiBoc-2,2′-biaziridine with grignard reagents
Publisher: American Chemical Society (ACS)
Date: 07-05-2015
Abstract: The copper-catalyzed ring opening of chiral-pool-derived 1,1'-diBoc-2,2'-biaziridine with Grignard reagents affords enantiopure 2-imidazolidinones in a desymmetrizing, cascade process involving the Boc protecting group. This ergent strategy provides reaction-ready, N-differentiated products and allows two C-C bond constructions concurrent to imidazolidinone formation. A variety of alkyl, cyclic, and aryl Grignard reagents are tolerated in reasonable to good yields.
Facile Synthesis and Preliminary Structure–Activity Analysis of New Sulfonamides Against Trypanosoma brucei
Publisher: American Chemical Society (ACS)
Date: 18-03-2014
DOI: 10.1021/ML400487T
The Role of the HPA Axis in Psychiatric Disorders and CRF Antagonists as Potential Treatments
Publisher: Wiley
Date: 07-2006
Abstract: An overview of the links between the Hypothalamic-Pituitary-Adrenal (HPA) axis and psychiatric disorders is presented. The current treatments are outlined, indicating that they are insufficient to meet the needs of those that suffer from these affective disorders. Therefore, there is an urgent need for the generation of new therapeutics, in particular, against new targets. The association of the corticotrophin releasing factor (CRF) and the HPA axis indicates that CRF antagonists should be beneficial as potential therapeutics.
Erratum to “A new protoberberine alkaloid from Meconopsis simplicifolia (D. Don) Walpers with potent antimalarial activity against a multidrug resistant Plasmodium falciparum strain” [J. Ethnopharmaco
Publisher: Elsevier BV
Date: 05-2014
Synthesis of Mono and Bis[60]fullerene-Based Dicationic Peptoids
Publisher: Wiley
Date: 21-11-2014
Phytochemical studies on the Australian native plant speciesAcacia pycnanthaandJacaranda mimosifoliaD.Don
Publisher: Informa UK Limited
Date: 11-06-2018
DOI: 10.1080/14786419.2018.1483922
Abstract: In ongoing investigations into colours in Nature, the chemical constituents from the flowers
Discovery of Potent Dual-Tailed Benzenesulfonamide Inhibitors of Human Carbonic Anhydrases Implicated in Glaucoma and in Vivo Profiling of Their Intraocular Pressure-Lowering Action
Publisher: American Chemical Society (ACS)
Date: 07-02-2020
Phytochemistry and Pharmacology of Medicinal Plants Used by the Tenggerese Society in Java Island of Indonesia
Publisher: MDPI AG
Date: 03-11-2022
DOI: 10.3390/MOLECULES27217532
Abstract: The archipelagic country of Indonesia is inhabited by 300 ethnic groups, including the indigenous people of Tengger. Based on the reported list of medicinal plants used by the Tengger community, we have reviewed each of them for their phytochemical constituents and pharmacological activities. Out of a total of 41 medicinal plants used by the Tengerrese people, 33 species were studied for their phytochemical and pharmacological properties. More than 554 phytochemicals with erse molecular structures belonging to different chemical classes including flavonoids, terpenoids, saponins and volatiles were identified from these studied 34 medicinal plants. Many of these medicinal plants and their compounds have been tested for various pharmacological activities including anti-inflammatory, antimicrobial, wound healing, headache, antimalarial and hypertension. Five popularly used medicinal plants by the healers were Garcinia mangostana, Apium graveolens, Cayratia clematidea, Drymocallis arguta and Elaeocarpus longifolius. Only A. graviolens were previously studied, with the outcomes supporting the pharmacological claims to treat hypertension. Few unexplored medicinal plants are Physalis lagascae, Piper lum, Rosa tomentosa and Tagetes tenuifolia, and they present great potential for biodiscovery and drug lead identification.
Reactions of electron-rich indoles with triflic anhydride
Publisher: Elsevier BV
Date: 05-2009
Anti-Infective and Anti-Cancer Properties of the Annona Species: Their Ethnomedicinal Uses, Alkaloid Diversity, and Pharmacological Activities
Publisher: MDPI AG
Date: 03-12-2019
DOI: 10.3390/MOLECULES24234419
Abstract: Annona species have been a valuable source of anti-infective and anticancer agents. However, only limited evaluations of their alkaloids have been carried out. This review collates and evaluates the biological data from extracts and purified isolates for their anti-infective and anti-cancer activities. An isoquinoline backbone is a major structural alkaloid moiety of the Annona genus, and more than 83 alkaloids have been isolated from this genus alone. Crude extracts of Annona genus are reported with moderate activities against Plasmodium falciparum showing larvicidal activities. However, no pure compounds from the Annona genus were tested against the parasite. The methanol extract of Annona muricata showed apparent antimicrobial activities. The isolated alkaloids from this genus including liriodenine, anonaine, asimilobine showed sensitivity against Staphylococcus epidermidis. Other alkaloids such as (+)-Xylopine and isocoreximine indicated significant anti-cancer activity against A549 and K-562 cell lines, respectively. This review revealed that the alkaloids from Annona genus are rich in structural ersity and pharmacological activities. Further exploration of this genus and their alkaloids has potential for developing novel anti-infective and anticancer drugs.
The Cascade Reactions of Indigo with Propargyl Substrates for Heterocyclic and Photophysical Diversity
Publisher: Wiley
Date: 12-02-2021
Abstract: The synthesis of structurally erse heterocycles for chemical space exploration was achieved via the cascade reactions of indigo with propargylic electrophiles. New pyrazinodiindolodione, naphthyridinedione, azepinodiindolone, oxazinoindolone and pyrrolodione products were prepared in one pot reactions by varying the leaving group (‐Cl, ‐Br, ‐OMs, ‐OTs) or propargyl terminal functionality (‐H, ‐Me, ‐Ph, ‐Ar). Mechanistic and density functional theory studies revealed that the unsaturated propargyl moiety can behave as an electrophile when aromatic terminal substitutions are made, and therefore competes with leaving group substitution for new outcomes. Selected products from the cascade reactions were investigated for their absorption and fluorescence properties, including transient absorption spectroscopy. This revealed polarity dependent excited state relaxation pathways, fluorescence, and triplet formation, thus highlighting these reactions as a means to access erse functional materials rapidly.
Anilinopyrimidines as novel antituberculosis agents
Publisher: Elsevier BV
Date: 05-2003
DOI: 10.1016/S0960-894X(03)00241-5
Abstract: A selection of novel anilinopyrimidine analogues have been found to have micromolar activity against Mycobacterium tuberculosis. This could potentially generate new lead compounds in the fight against multi-drug resistant tuberculosis.
An improved synthesis of pyrido[2,3-d]pyrimidin-4(1H)-ones and their antimicrobial activity
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8OB00627J
Abstract: The screening of a small chemical library showed 2-thioxodihydropyrido[2,3- d ]pyrimidine 10a had broad spectrum antibacterial activity (MIC 0.49–3.9 μg mL −1 ), and reasonable antifungal activity (MIC 31.25 μg mL −1 ).
Control of HIV through the inhibition of HIV-1 integrase: a medicinal chemistry perspective
Publisher: Bentham Science Publishers Ltd.
Date: 03-2007
DOI: 10.2174/157340607780059558
Abstract: This article reviews the current status of classes of HIV-1 integrase enzyme inhibitors. These classes include peptide-based inhibitors, natural products, polyhydroxylated aromatics, diketo acids, naphthyridines, and sulfonated compounds including sulfonic acids. Discussions of structure activity relationships are presented and include the current overview of the structure-based model, suitable for the further design and development. To date, the advances in the medicinal chemistry of HIV-1 integrase inhibitors have relied mostly on ligand-based designs leading to most displaying similar binding interactions within the active site or at the dimer interface. This paves the way for single enzyme mutations rendering entire compound classes inactive and thus, the requirement for second and third generation inhibitors with novel modes of binding is apparent. To facilitate future structure-based drug design efforts, a model of the biologically relevant structure of the HIV-1 integrase enzyme, a dimer of dimers has also been discussed.
Synthesis and antibacterial activity of C2-symmetric binaphthyl scaffolded amino acid derivatives
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.EJMECH.2011.06.024
Abstract: The synthesis of eleven novel antibacterial agents is reported. The structures are based on a C(2)-symmetric binaphthyl scaffold which holds two identical chains consisting of a short linker, a basic amino acid and a small hydrophobic side chain. Antibacterial activity is revealed for a number of derivatives down to an MIC of 2 μg/mL (2 μM) against Staphylococcus aureus--comparable to vancomycin, and an MIC of 31 μg/mL (31 μM) against some vancomycin-resistant enterococcal strains.
Body Odor and Sex: Do Cuticular Hydrocarbons Facilitate Sexual Attraction in the Small Hairy Maggot Blowfly?
Publisher: Springer Science and Business Media LLC
Date: 03-2018
DOI: 10.1007/S10886-018-0943-3
Abstract: Cuticular hydrocarbons (CHCs) play an important role as contact pheromones in insects, particularly in flies. However, for many fly taxa our understanding of the importance of CHCs in sexual communication is limited. Within the family Calliphoridae (blowflies), sex-specific differences in CHCs have been reported for several species, but there is no evidence that CHCs facilitate sexual behavior. In order to elucidate the function of CHCs in Calliphoridae, studies combining behavioral and chemical analyses are required. The present study used gas chromatography/mass spectrometry, along with behavioral assays, to assess whether CHCs facilitate sexual attraction in the small hairy maggot blowfly, Chrysomya varipes. The specific aims were to: 1) determine if CHCs differ between the sexes and 2) assess whether flies exhibit positive chemotaxis to CHCs of the opposite sex. Fifty-two hydrocarbons common to both sexes were identified, and quantitative differences for numerous CHCs were observed between the sexes. However, behavioral assays provided no evidence that flies were attracted to CHCs of the opposite sex, challenging the hypothesis that CHCs facilitate sexual attraction in Ch. varipes. In contrast to other blowflies, Ch. varipes males invest heavily in courtship displays and ornamentation, so we speculate that visual communication in this species may have relaxed sexual selection for chemical communication. More broadly, our findings support suggestions that CHCs may not always facilitate insect sexual communication.
Antarctic Moss Biflavonoids Show High Antioxidant and Ultraviolet-Screening Activity
Publisher: American Chemical Society (ACS)
Date: 07-08-2017
DOI: 10.1021/ACS.JNATPROD.7B00085
Abstract: Ceratodon purpureus is a cosmopolitan moss that survives some of the harshest places on Earth: from frozen Antarctica to hot South Australian deserts. In a study on the survival mechanisms of the species, nine compounds were isolated from Australian and Antarctic C. purpureus. This included five biflavonoids, with complete structural elucidation of 1 and 2 reported here for the first time, as well as an additional four known phenolic compounds. Dispersion-corrected DFT calculations suggested a rotational barrier, leading to atropisomerism, resulting in the presence of diastereomers for compound 2. All isolates absorbed strongly in the ultraviolet (UV) spectrum, e.g., biflavone 1 (UV-A, 315-400 nm), which displayed the strongest radical-scavenging activity, 13% more efficient than the standard rutin p-coumaric acid and trans-ferulic acid showed the highest UV-B (280-315 nm) absorption. The more complex and abundant 1 and 2 presumably have dual roles as both UV-screening and antioxidant compounds. They are strongly bound to Antarctic moss cell walls as well as located inside the cells of moss from both locations. The combined high stability and photoprotective abilities of these isolates may account for the known resilience of this species to UV-B radiation and its survival in some of the toughest locations in the world.
Synthesis of novel N-protected hydrophobic phenylalanines and their application in potential antibacterials
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.EJMECH.2008.07.001
Abstract: An efficient synthesis of two new N-acetyl-4'-arylphenylalanines is described together with their incorporation into a number of cationic peptoid antibacterial agents, one of which had an MIC of 7.8 microg/mL against Staphylococcus aureus.
Substitution, oxidation and addition reactions at C-7 of activated indoles
Publisher: Elsevier BV
Date: 1994
Flowers in Australia: Phytochemical Studies on the Illawarra Flame Tree and Alstonville
Publisher: CSIRO Publishing
Date: 2016
DOI: 10.1071/CH16058
Abstract: The first reported phytochemical studies on two species of flowers in Australia enabled the identification of six secondary metabolites from Illawarra flame tree flower (Brachychiton acerifolius) and seven secondary metabolites from the flowers of the Alstonville (Tibouchina lepidota). Pelargonidin 3-(6-coumarylglucoside)-5-(6-acetylglucoside) was found to be responsible for the red colour of B. acerifolius, whereas malvidin 3-(coumarylglucoside)-5-(acetylxyloside) was responsible for the purple colour of (T. lepidota) flowers. (2S)-4,5-Dihydroxyflavanone 7-O-β-d-glucuronide methyl ester was isolated for the first time from B. acerifolius, and its absolute configuration was determined by circular dichroism spectroscopy. Some of the traditional uses of B. acerifolius could also be correlated with the known activity of the isolated metabolites.
The Synthesis and Testing of Arenearylpyrimidylmethanes as Antimalarial Agents
Publisher: Wiley
Date: 30-06-2006
Cover Feature: The Cascade Reactions of Indigo with Propargyl Substrates for Heterocyclic and Photophysical Diversity (Chem. Eur. J. 11/2021)
Publisher: Wiley
Date: 22-12-2020
A new protoberberine alkaloid from Meconopsis simplicifolia (D. Don) Walpers with potent antimalarial activity against a multidrug resistant Plasmodium falciparum strain
Publisher: Elsevier BV
Date: 12-2013
DOI: 10.1016/J.JEP.2013.09.052
Abstract: The aerial components of Meconopsis simplicifolia (D. Don) Walpers are indicated in Bhutanese traditional medicine for treating malaria, coughs and colds, and the infections of the liver, lung and blood. This study is to validate the ethnopharmacological uses of this plant and also identify potent antimalarial drug leads through bioassays of its crude extracts and phytochemical constituents. Meconopsis simplicifolia (D. Don) Walpers was collected from Bhutan and its crude MeOH extract was subjected to acid-base fractionation. Through repeated extractions, separations and spectroscopic analysis, the alkaloids obtained were identified and tested for their antimalarial and cytotoxicity activities. Phytochemical studies resulted in the isolation of one new protoberberine type alkaloid which we named as simplicifolianine and five known alkaloids: protopine, norsanguinarine, dihydrosanguinarine, 6-methoxydihydrosanguinarine and oxysanguinarine. Among the five of the alkaloids tested, simplicifolianine showed the most potent antiplasmodial activities against the Plasmodium falciparum strains, TM4/8.2 (chloroquine-antifolate sensitive strain) and K1CB1 (multidrug resistant strain) with IC50 values of 0.78 μg/mL and 1.29 μg/mL, respectively. The compounds tested did not show any significant cytotoxicity activities against human oral carcinoma KB cells and normal Vero cells of African kidney epithelial cells. This study validated the traditional uses of the plant for the treatment of malaria and identified a new alkaloid, simplicifolianine as a potential antimalarial drug lead.
Cationic Peptidomimetic Amphiphiles Having a N-Aryl- or N-Naphthyl-1,2,3-Triazole Core Structure Targeting Clostridioides (Clostridium) difficile: Synthesis, Antibacterial Evaluation, and an In Vivo C. difficile Infection Model
Publisher: MDPI AG
Date: 26-07-2021
DOI: 10.3390/ANTIBIOTICS10080913
Abstract: Clostridioides (also known as Clostridium) difficile is a Gram-positive anaerobic, spore producing bacterial pathogen that causes severe gastrointestinal infection in humans. The current chemotherapeutic options are inadequate, expensive, and limited, and thus inexpensive drug treatments for C. difficile infection (CDI) with improved efficacy and specificity are urgently needed. To improve the solubility of our cationic hiphilic 1,1′-binaphthylpeptidomimetics developed earlier that showed promise in an in vivo murine CDI model we have synthesized related compounds with an N-arytriazole or N-naphthyltriazole moiety instead of the 1,1′-biphenyl or 1,1′-binaphthyl moiety. This modification was made to increase the polarity and thus water solubility of the overall peptidomimetics, while maintaining the aromatic character. The dicationic N-naphthyltriazole derivative 40 was identified as a C. difficile-selective antibacterial with MIC values of 8 µg/mL against C. difficile strains ATCC 700057 and 132 (both ribotype 027). This compound displayed increased water solubility and reduced hemolytic activity (32 µg/mL) in an in vitro hemolysis assay and reduced cytotoxicity (CC50 32 µg/mL against HEK293 cells) relative to lead compound 2. Compound 40 exhibited mild efficacy (with 80% survival observed after 24 h compared to the DMSO control of 40%) in an in vivo murine model of C. difficile infection by reducing the severity and slowing the onset of disease.
An assessment of the Bhutanese traditional medicine for its ethnopharmacology, ethnobotany and ethnoquality: Textual understanding and the current practices
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.JEP.2013.04.030
Abstract: : This study involves the assessment of the Bhutanese traditional medicine (BTM) which was integrated with the mainstream biomedicine in 1967 to provide primary health care services in the country. It caters to 20-30% of the daily out-patients within 49 traditional medicine units attached to 20 district modern hospitals and 29 Basic Health Units in the country. : This study presents the ethnopharmacological, ethnobotanical and the ethnoquality concepts in relation to mainstream Tibetan medicine and describes the current practices of BTM. : Experienced BTM practitioners (Drung-tshos and Smen-pas) were selected using a convenience s ling method and were interviewed using an open questionnaire followed by informal discussions. The corpus of BTM, Tibetan and scientific literature was obtained and the information on ethnopharmacological, ethnoquality and ethnobotanical concepts and current practices of BTM was extracted. : This study found that the BTM shares many similarities in terms of materia medica, pharmacopoeia and the principles and concepts of ethnopharmacology and ethnobotany with its mainstream Tibetan medicine. However, the resourceful Bhutanese Drung-tshos and Smen-pas have adapted this medical system based on the local language, culture, disease trend, health care needs and their familiarity with the locally available medicinal ingredients making it particular to the country. A number of notable distinctions observed in the current practices include a code of classification of diseases (only 79 of 404 types of disorders recognized), formulations (currently used only 103 of thousands formulation types), usage of medicinal plants (only 229 species of thousands described) and selected treatment procedures (golden needle and water therapy). This BTM was found to cater to 20-30% of daily out-patients visiting 49 modern hospitals and basic health units in the country. : The BTM has been evolved from the Tibetan medicine. While the pharmacopoeia, ethnopharmacology, ethnobotany and the ethnoquality aspects shares commonalities with the mainstream Tibetan medicine, there are some practices unique to BTM. Such uniqueness observed in the current practices of BTM include formulations, medicinal plants collection and usage, and the treatment procedures including golden needle and water therapy. This could be a promising source of information for the rediscovery of useful remedies, the development of modern phytotherapeutics and the establishment of efficient quality control measures.
Pharmacophore Development for Corticotropin-Releasing Hormone: New Insights into Inhibitor Activity
Publisher: American Chemical Society (ACS)
Date: 08-06-1999
DOI: 10.1021/JM9900117
Indonesian marine and its medicinal contribution
Publisher: Springer Science and Business Media LLC
Date: 16-10-2023
Oxidative coupling of indoles using thallium(III) trifluoroacetate
Publisher: Elsevier BV
Date: 08-2008
Bioactive glycosides from the African medicinal plantBoerhavia erectaL.
Publisher: Informa UK Limited
Date: 20-02-2015
DOI: 10.1080/14786419.2015.1013470
Abstract: Phytochemical studies of the previously unexplored stem of Boerhavia erecta from Burkina Faso, resulted in the isolation of an unreported glycoside 4, 2,3-dihydroxypropylbenzoate-3-O-β-[4″-methoxy] glucuronide as well as seven known glycosides (1-3, 5-8). The major isolate 5 and 8 indicated a significant inhibition against HIV integrase (IC50 10 and 22 μg/mL, respectively). The extracts and isolates were also tested for anti-malarial activity, but insignificant activity was observed.
Novel spiro and fused heterocycles from the allylation of indigo
Publisher: Elsevier BV
Date: 12-2009
Synthesis and antibacterial studies of binaphthyl-based tripeptoids. Part 2
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.BMC.2010.05.005
Abstract: A compact synthesis of 15 new binaphthyl-based dicationic tripeptoids and one biphenyl based dicationic tripeptoid is described. Fourteen of these tripeptoids resulted from variation of the C-2' ether substituent of the binaphthyl unit. An O-iso-butyl ether binaphthyl derivative was found to be the most active against Staphylococcus aureus (MIC 1.95 μg/mL). The biphenyl analogue also showed good activity against S. aureus (MIC 1.95 μg/mL). These compounds, however, were less active against four vancomycin-resistant strains of enterococci (VRE) than some of our previously developed compounds that had an O-iso-pentyl ether substituent on the binaphthyl unit and a C-2 L-Leu moiety.
A twist of nature – the significance of atropisomers in biological systems
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C4NP00121D
Abstract: This review encompasses the synthesis and identification of recently detected natural atropisomers with potential therapeutic activity.
Discovery of in silico hits targeting the nsP3 macro domain of chikungunya virus
Publisher: Springer Science and Business Media LLC
Date: 23-04-2014
The Detosylation of Chiral 1,2-Bis(tosylamides)
Publisher: American Chemical Society (ACS)
Date: 21-06-2021
A new strategy for the stereoselective synthesis of 2,2′-bipyrrolidines
Publisher: Elsevier BV
Date: 08-2009
How To Make Nitroaromatic Compounds Glow: Next‐Generation Large X‐Shaped, Centrosymmetric Diketopyrrolopyrroles
Publisher: Wiley
Date: 10-07-2020
Diterpenoid alkaloids of Aconitum laciniatum and mitigation of inflammation by 14-O-acetylneoline in a murine model of ulcerative colitis
Publisher: Springer Science and Business Media LLC
Date: 04-08-2015
DOI: 10.1038/SREP12845
Abstract: Aconitum laciniatum is used in Bhutanese traditional medicine for treating various chronic infections and inflammatory conditions. We carried out in-depth isolation and characterization of the phytochemicals from the root component and determined the anti-inflammatory effects of the isolated compounds against chemically-induced colitis in mice. Five diterpenoid alkaloids - pseudaconitine, 14-veratroylpseudaconine, 14- O -acetylneoline, neoline and senbusine A - were isolated from A. laciniatum for the first time. Two of the alkaloids were tested for anti-inflammatory properties in the TNBS-induced colitis model in mice. Various parameters were measured to assess pathology including weight loss, clinical and macroscopic scores, histological structure and IFN-γ production in the gut. Of the two alkaloids tested, 14- O -acetylneoline showed significant protection against different parameters of colitic inflammation. Compared to control mice that received TNBS alone, mice treated with 14- O -acetylneoline experienced significantly less weight loss and had significantly lower clinical scores, macroscopic pathology and grades of histological inflammation. Moreover, colonic IFN-γ mRNA levels were significantly reduced in mice that received 14- O -acetylneoline compared to control mice that received TNBS alone. This alkaloid is now considered a novel anti-colitis drug lead compound.
Synthesis and structure–activity relationship (SAR) studies of 1,2,3-triazole, amide, and ester-based benzothiazole derivatives as potential molecular probes for tau protein
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2MD00358A
Abstract: A series of tau ligands was synthesized replacing the photoisomerisable trans -diene bridge of PBB3 with 1,2,3-triazole, amide, and ester moieties. Several ligands were able to visualise Aβ plaques and neurofibrillary tangles in Alzheimer's disease.
Ethnobotanical authentication and identification of Khrog-sman (Lower Elevation Medicinal Plants) of Bhutan
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.JEP.2011.01.034
Abstract: The Bhutanese form of g.so-ba-rig-pa medicine, which is a scholarly medical system, belongs to a larger system of medicinal corpus that spreads from Mongolia to India. It uses medicinal plants as a bulk ingredient but only 'Higher Elevation Medicinal Plants' have been botanically identified so far. Our study reports the botanical identification of 'Lower Elevation Medicinal Plants' and their ethnomedical uses. To botanically identify the 'Lower Elevation Medicinal Plants' used in Bhutanese traditional medicine. A five stage process was conducted which consisted of: (1) a survey of specialized ancient ethnomedical literatures (Pharmacopoeias and formularies) (2) freely listing the 'Lower Elevation Medicinal Plants' reported in the ancient Bhutanese medical texts and translating their ethnomedical uses in equivalent terms of English (3) making field visits, collecting herbarium specimens and photographs, and spot identification of plants (4) double blind testing of Bhutanese traditional medicine practitioners for authentication and standardization of Bhutanese g.so-ba-rig-pa names (5) organising workshops for open forum discussions on medicinal plants involving Traditional Physicians and other professional participants of the relevant areas. We identified the botanical names of 113 'Lower Elevation Medicinal Plants' belonging to 68 families and 104 genera. Out of 113 medicinal plant species identified, 92 species are currently used in Bhutan and the remaining 21 species were not used in the current formulation, but described in the Bhutanese traditional medical texts. The identification of these 21 species was achieved both ethnomedically and botanically for the first time. Out of the 28 plant species that are currently imported from India, we found for the first time, even to the knowledge of Traditional Physicians, that 16 of them are actually growing abundantly in Bhutan. Among the plant parts collected, seeds were the most prominent followed by fruits and then roots. Our study identified 113 'Lower Elevation Medicinal Plants' out of which 92 of them are used daily in formulating 102 multi-ingredient prescription medicines in Bhutan.
Regioselective Synthesis of Novele-Edge-[60]fullerenylmethanodihydropyrroles and 1,2-Dihydromethano[60]fullerenes
Publisher: Wiley
Date: 12-2005
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