ORCID Profile
0000-0002-8341-7754
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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 | Natural Products Chemistry | Biological And Medical Chemistry | Organic Chemistry | Animal Protection (Pests and Pathogens) | Cheminformatics and Quantitative Structure-Activity Relationships | Bioinformatics | Biologically active molecules | Biochemistry and Cell Biology | Microbiology Not Elsewhere Classified | Organic Chemical Synthesis | Microbiology | Nanochemistry and Supramolecular Chemistry | Chemical Characterisation of Materials | Plant Biology | Structural Biology (incl. Macromolecular Modelling) | Systems Biology | Environmental biotechnology | Analytical Biochemistry | Organic Chemistry Not Elsewhere Classified | Protein Targeting And Signal Transduction | Membrane Biology | Microbial Systematics, Taxonomy And Phylogeny | Neurosciences Not Elsewhere Classified | Natural products and bioactive compounds | Characterisation of Biological Macromolecules | Macromolecular and Materials Chemistry | Inorganic Chemistry | Biotechnology Not Elsewhere Classified | Animal Production | Proteins and Peptides | Plant Cell and Molecular Biology | Inorganic Chemistry Not Elsewhere Classified | Plant Physiology | Infectious Diseases | Biodiscovery |
ANZSRC Socio-Economic Objective (SEO)
Treatments (e.g. chemicals, antibiotics) | Cancer and related disorders | Expanding Knowledge in the Chemical Sciences | Biological sciences | Expanding Knowledge in the Biological Sciences | Grain Legumes | Human Biological Preventatives (e.g. Vaccines) | Human Diagnostics | Chemical sciences | Other environmental aspects | Soybeans | Animal Welfare | Infectious diseases | Animal Protection Chemicals | Nervous system and disorders | Cardiovascular system and diseases | Human Pharmaceutical Treatments (e.g. Antibiotics) | Treatments (e.g. chemicals, antibiotics)
Related Links
Publications
Dual inhibition of DNA polymerase PolC and protein tyrosine phosphatase CpsB uncovers a novel antibiotic target
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.BBRC.2012.11.049
Abstract: Increasing antibiotic resistance is making the identification of novel antimicrobial targets critical. Recently, we discovered an inhibitor of protein tyrosine phosphatase CpsB, fascioquinol E (FQE), which unexpectedly inhibited the growth of Gram-positive pathogens. CpsB is a member of the polymerase and histidinol phosphate phosphatase (PHP) domain family. Another member of this family found in a variety of Gram-positive pathogens is DNA polymerase PolC. We purified the PHP domain from PolC (PolC(PHP)), and showed that this competes away FQE inhibition of CpsB phosphatase activity. Furthermore, we showed that this domain hydrolyses the 5'-p-nitrophenyl ester of thymidine-5'-monophosphate (pNP-TMP), which has been used as a measure of exonuclease activity. Finally, we showed that FQE not only inhibits the phosphatase activity of CpsB, but also ability of PolC(PHP) to catalyse the hydrolysis of pNP-TMP. This suggests that PolC may be the essential target of FQE, and that the PHP domain may represent an as yet untapped target for the development of novel antibiotics.
Viridicatumtoxins: Expanding on a Rare Tetracycline Antibiotic Scaffold
Publisher: American Chemical Society (ACS)
Date: 07-12-2015
Abstract: Viridicatumtoxins, which belong to a rare class of fungal tetracycline-like mycotoxins, were subjected to comprehensive spectroscopic and chemical analysis, leading to reassignment/assignment of absolute configurations and characterization of a remarkably acid-stable antibiotic scaffold. Structure activity relationship studies revealed exceptional growth inhibitory activity against vancomycin-resistant Enterococci (IC50 40 nM), >270-fold more potent than the commercial antibiotic oxytetracycline.
Waspergillamide A, a Nitro depsi-Tetrapeptide Diketopiperazine from an Australian Mud Dauber Wasp-Associated Aspergillus sp. (CMB-W031).
Publisher: American Chemical Society (ACS)
Date: 24-02-2017
DOI: 10.1021/ACS.JNATPROD.6B01062
Abstract: Chemical profiling of extracts from a mud dauber wasp-associated fungus, Aspergillus sp. (CMB-W031), revealed a remarkably erse array of secondary metabolites, with many biosynthetic gene clusters being transcriptionally responsive to specific culture conditions. Chemical fractionation of a jasmine rice cultivation yielded many known fungal metabolites, including the highly cytotoxic (-)-stephacidin B and an unprecedented nonribosomal peptide synthase derived nitro depsi-tetrapeptide diketopiperazine, waspergillamide A (1). All structures were assigned by detailed spectroscopic analysis and, where appropriate, chemical degradation and Marfey's analysis.
Dragmacidins: New Protein Phosphatase Inhibitors from a Southern Australian Deep-Water Marine Sponge, Spongosorites sp.
Publisher: American Chemical Society (ACS)
Date: 05-1998
DOI: 10.1021/NP970483T
Noonindoles G–L: Indole Diterpene Glycosides from the Australian Marine-Derived Fungus Aspergillus noonimiae CMB-M0339
Publisher: American Chemical Society (ACS)
Date: 20-01-2023
Oligomycins as inhibitors of K-Ras plasma membrane localisation
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C5OB02020D
Abstract: Rare oligomycins from soil-derived Streptomyces are low nM inhibitors of K-Ras plasma membrane localisation.
Trivirensols: Selectively Bacteriostatic Sesquiterpene Trimers from the Australian Termite Nest-Derived Fungus Trichoderma virens CMB-TN16
Publisher: American Chemical Society (ACS)
Date: 18-10-2019
DOI: 10.1021/ACS.JNATPROD.9B00760
Abstract: The termite nest-derived fungus
Staurosporines Disrupt Phosphatidylserine Trafficking and Mislocalize Ras Proteins
Publisher: Elsevier BV
Date: 12-2012
Levofloxacin and Indolicidin for Combination Antimicrobial Therapy
Publisher: Bentham Science Publishers Ltd.
Date: 10-03-2015
DOI: 10.2174/1567201811666140910094050
Abstract: Despite the increasing need for antibiotics to fight infectious diseases, fewer new antibiotics are available on the market. Unfortunately, developing a new class of antibiotics is associated with high commercial risk. Therefore, modification or combination of existing antibiotics to improve their efficacy is a promising strategy. Herein, we conjugated the antibiotic, levofloxacin, with two peptides, i.e. an antimicrobial peptide indolicidin and a cell penetrating peptide (TAT). Glycolic acid and glycine linkers were used between levofloxacin and peptides. We developed an optimized condition for coupling of levofloxacin via its carboxylic group to glycolic acid using solid phase peptide synthesis (SPPS). Antibacterial and haemolytic assays were carried out on the conjugates and only the levofloxacin-indolicidin conjugate demonstrated moderate antibacterial activity. Interestingly, physical mixture of levofloxacin and indolicidin showed improvement in the activity against Gram-positive bacteria.
Rare Streptomyces N-formyl amino-salicylamides inhibit oncogenic K-Ras
Publisher: American Chemical Society (ACS)
Date: 19-09-2014
DOI: 10.1021/OL502376E
Sydowiols A–C: Mycobacterium tuberculosis protein tyrosine phosphatase inhibitors from an East China Sea marine-derived fungus, Aspergillus sydowii
Publisher: Elsevier BV
Date: 11-2013
Ikirydinium A: a new indole alkaloid from the seeds of Hunteria umbellata (K. Schum)
Publisher: Elsevier BV
Date: 12-2011
Chrysosporazines F–M: P-Glycoprotein Inhibitory Phenylpropanoid Piperazines from an Australian Marine Fish Derived Fungus, Chrysosporium sp. CMB-F294
Publisher: American Chemical Society (ACS)
Date: 24-01-2020
DOI: 10.1021/ACS.JNATPROD.9B01181
Abstract: Chemical analysis of the fungus
New from Old: Thorectandrin Alkaloids in a Southern Australian Marine Sponge, Thorectandra choanoides (CMB-01889)
Publisher: MDPI AG
Date: 09-02-2021
DOI: 10.3390/MD19020097
Abstract: Thorectandra choanoides (CMB-01889) was prioritized as a source of promising new chemistry from a library of 960 southern Australian marine sponge extracts, using a global natural products social (GNPS) molecular networking approach. The sponge was collected at a depth of 45 m. Chemical fractionation followed by detailed spectroscopic analysis led to the discovery of a new tryptophan-derived alkaloid, thorectandrin A (1), with the GNPS cluster revealing a halo of related alkaloids 1a–1n. In considering biosynthetic origins, we propose that Thorectandrachoanoides (CMB-01889) produces four well-known alkaloids, 6-bromo-1′,8-dihydroaplysinopsin (2), 6-bromoaplysinopsin (3), aplysinopsin (4), and 1′,8-dihydroaplysinopsin (10), all of which are susceptible to processing by a putative indoleamine 2,3-dioxygenase-like (IDO) enzyme to 1a–1n. Where the 1′,8-dihydroalkaloids 2 and 10 are fully transformed to stable ring-opened thorectandrins 1 and 1a–1b, and 1h–1j, respectively, the conjugated precursors 3 and 4 are transformed to highly reactive Michael acceptors that during extraction and handling undergo complete transformation to artifacts 1c–1g, and 1k–1n, respectively. Knowledge of the susceptibility of aplysinopsins as substrates for IDOs, and the relative reactivity of Michael acceptor transformation products, informs our understanding of the pharmaceutical potential of this vintage marine pharmacophore. For ex le, the cancer tissue specificity of IDOs could be exploited for an immunotherapeutic response, with aplysinopsins transforming in situ to Michael acceptor thorectandrins, which covalently bind and inhibit the enzyme.
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.
Glenthmycins A–M: Macrocyclic Spirotetronate Polyketide Antibacterials from the Australian Pasture Plant-Derived Streptomyces sp. CMB-PB041
Publisher: American Chemical Society (ACS)
Date: 31-05-2022
DOI: 10.1021/ACS.JNATPROD.2C00444
Abstract: Chemical investigation of Australian pasture plant-derived
Roseopurpurins: Chemical Diversity Enhanced by Convergent Biosynthesis and Forward and Reverse Michael Additions
Publisher: American Chemical Society (ACS)
Date: 18-08-2016
DOI: 10.1021/ACS.ORGLETT.6B02099
Abstract: Cultures of the estuarine fungus Penicillium roseopurpureum (CMB-MF038) yielded a erse array of polyketides, many of which were related via a highly convergent biosynthetic pathway. In addition to revising and assigning structures, and documenting chemical and biological properties, pro-drug cytotoxic properties were attributed to roseopurpurins H (10) and I (11) on the basis of in situ reverse Michael addition to a cytotoxic Michael acceptor (12).
A galloylated cyanogenic glycoside from the Australian endemic rainforest tree Elaeocarpus sericopetalus (Elaeocarpaceae)
Publisher: Elsevier BV
Date: 07-2006
DOI: 10.1016/J.PHYTOCHEM.2006.03.022
Abstract: A cyanogenic glycoside - 6'-O-galloylsambunigrin - has been isolated from the foliage of the Australian tropical rainforest tree species Elaeocarpus sericopetalus F. Muell. (Elaeocarpaceae). This is the first formal characterisation of a cyanogenic constituent in the Elaeocarpaceae family, and only the second in the order Malvales. 6'-O-galloylsambunigrin was identified as the principal glycoside, accounting for 91% of total cyanogen in a leaf methanol extract. Preliminary analyses indicated that the remaining cyanogen content may comprise small quantities of sambunigrin, as well as di- and tri-gallates of sambunigrin. E. sericopetalus was found to have foliar concentrations of cyanogenic glycosides among the highest reported for tree leaves, up to 5.2 mg CN g(-1) dry wt.
Development of Multilayer Nanoparticles for the Delivery of Peptide-Based Subunit Vaccine against Group A Streptococcus
Publisher: MDPI AG
Date: 10-10-2022
DOI: 10.3390/PHARMACEUTICS14102151
Abstract: Peptide-based subunit vaccines include only minimal antigenic determinants, and, therefore, are less likely to induce allergic immune responses and adverse effects compared to traditional vaccines. However, peptides are weakly immunogenic and susceptible to enzymatic degradation when administered on their own. Hence, we designed polyelectrolyte complex (PEC)-based delivery systems to protect peptide antigens from degradation and improve immunogenicity. Lipopeptide (LCP-1) bearing J8 B-cell epitope derived from Group A Streptococcus (GAS) M-protein was selected as the model peptide antigen. In the pilot study, LCP-1 incorporated in alginate/cross-linked polyarginine-J8-based PEC induced high J8-specific IgG antibody titres. The PEC system was then further modified to improve its immune stimulating capability. Of the formulations tested, PEC-4, bearing LCP-1, alginate and cross-linked polylysine, induced the highest antibody titres in BALB/c mice following subcutaneous immunisation. The antibodies produced were more opsonic than those induced by mice immunised with other PECs, and as opsonic as those induced by antigen adjuvanted with powerful complete Freund’s adjuvant.
Poly(hydrophobic amino acid) Conjugates for the Delivery of Multiepitope Vaccine against Group A Streptococcus
Publisher: American Chemical Society (ACS)
Date: 11-08-2021
DOI: 10.1021/ACS.BIOCONJCHEM.1C00333
Abstract: Peptide-based vaccines are composed of small, defined, antigenic peptide epitopes. They are designed to induce well-controlled immune responses. Multiple epitopes are often employed in these vaccines to cover strain variability of a pathogen. However, peptide epitopes cannot stimulate adequate immune responses on their own and require an adjuvant (immune stimulant) and/or delivery system. Here, we designed and synthesized a multiepitope vaccine candidate against Group A Streptococcus (GAS) composed of several B-cell epitopes (J8, PL1, and 88/30) derived from GAS M-protein, universal PADRE T-helper cell epitope, and a polyleucine self-adjuvanting unit. The vaccine components were conjugated together (using mercapto-maleimide and azide-alkyne Huisgen cycloaddition reactions) or delivered as a mixture. The conjugated multiepitope vaccine candidate self-assembled into small nanoparticles and chain-like aggregated nanoparticles (CLANs) that were able to induce the production of J8-, PL1-, and 88/30-specific antibodies in mice. The multiepitope conjugate and the physical mixture of conjugates bearing the in idual epitopes produced similar nanoparticles and induced comparable immune responses. Hence, simple physical mixing can replace complex chemical conjugation to produce multiepitope nanoparticles with equivalent morphology and immunological efficacy. This greatly simplifies vaccine production.
Lamellarin O, a Pyrrole Alkaloid from an Australian Marine Sponge, Ianthella sp., Reverses BCRP Mediated Drug Resistance in Cancer Cells
Publisher: MDPI AG
Date: 27-06-2014
DOI: 10.3390/MD12073818
A search for kinase inhibitors and antibacterial agents: bromopyrrolo-2-aminoimidazoles from a deep-water Great Australian Bight sponge, Axinella sp.
Publisher: Elsevier BV
Date: 07-2012
Rare Streptomyces sp. polyketides as modulators of K-Ras localisation
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4OB00745J
Abstract: A rare class of oxanthromicin polyketides was isolated from a soil-derived Streptomyces sp. SAR-investigation showed that selected analogues can induce significant K-Ras plasma membrane mislocalisation and can synergise the K-Ras plasma membrane mislocalisation properties of staurosporine.
GluClR-mediated inhibitory postsynaptic currents reveal targets for ivermectin and potential mechanisms of ivermectin resistance
Publisher: Public Library of Science (PLoS)
Date: 29-01-2019
Talarophenol sulfate and talarophilones from the Australian mud dauber wasp-associated fungus, Talaromyces sp. CMB-W045
Publisher: Elsevier BV
Date: 10-2019
Talarolides Revisited: Cyclic Heptapeptides from an Australian Marine Tunicate-Associated Fungus, Talaromyces sp. CMB-TU011
Publisher: MDPI AG
Date: 11-09-2023
DOI: 10.3390/MD21090487
Cinerols, Nitrogenous Meroterpenoids from the Marine Sponge Dysidea cinerea
Publisher: American Chemical Society (ACS)
Date: 18-09-2019
DOI: 10.1021/ACS.JNATPROD.9B00471
Abstract: Eleven new nitrogenous meroterpenoids, cinerols A-K (
Wollamides: Antimycobacterial cyclic hexapeptides from an australian soil Streptomyces
Publisher: American Chemical Society (ACS)
Date: 17-09-2014
DOI: 10.1021/OL502472C
Abstract: A soil Streptomyces nov. sp. (MST-115088) isolated from semiarid terrain near Wollogorang Station, Queensland, returned two known and two new ex les of a rare class of cyclic hexapeptide, desotamides A and B (1 and 2) and E and F (3 and 4), respectively, together with two new d-Orn homologues, wollamides A and B (5 and 6). Structures were assigned by detailed spectroscopic and C3 Marfey's analysis. The desotamides/wollamides exhibit growth inhibitory activity against Gram-positive bacteria (IC50 0.6-7 μM) and are noncytotoxic to mammalian cells (IC50 >30 μM). The wollamides exhibit antimycobacterial activity (IC50 2.8 and 3.1 μM), including reduction in the intracellular mycobacterial survival in murine bone marrow-derived macrophages.
Ontogenetic Variation in the Chemical Defenses of Cane Toads (Bufo marinus): Toxin Profiles and Effects on Predators
Publisher: Springer Science and Business Media LLC
Date: 05-03-2009
DOI: 10.1007/S10886-009-9608-6
Abstract: We conducted a quantitative and qualitative chemical analysis of cane toad bufadienolides--the cardioactive steroids that are believed to be the principal cane toad toxins. We found complex shifts in toxin composition through toad ontogeny: (1) eggs contain at least 28 dominant bufadienolides, 17 of which are not detected in any other ontogenetic stage (2) tadpoles present a simpler chemical profile with two to eight dominant bufadienolides and (3) toxin ersity decreases during tadpole life but increases again after metamorphosis (larger metamorph/juvenile toads display five major bufadienolides). Total bufadienolide concentrations are highest in eggs (2.64 +/- 0.56 micromol/mg), decreasing during tadpole life stages (0.084 +/- 0.060 micromol/mg) before rising again after metamorphosis (2.35 +/- 0.45 micromol/mg). These variations in total bufadienolide levels correlate with toxicity to Australian frog species. For ex le, consumption of cane toad eggs killed tadpoles of two Australian frog species (Limnodynastes convexiusculus and Litoria rothii), whereas no tadpoles died after consuming late-stage cane toad tadpoles or small metamorphs. The high toxicity of toad eggs reflects components in the egg itself, not the surrounding jelly coat. Our results suggest a dramatic ontogenetic shift in the danger that toads pose to native predators, reflecting rapid changes in the types and amounts of toxins during toad development.
Heterofibrins: inhibitors of lipid droplet formation from a deep-water southern Australian marine sponge, Spongia (Heterofibria) sp.
Publisher: Royal Society of Chemistry (RSC)
Date: 2010
DOI: 10.1039/C003840G
Abstract: A bioassay-guided search for inhibitors of lipid droplet formation in a deep-water southern Australian marine sponge, Spongia (Heterofibria) sp., yielded six new compounds, fatty acids heterofibrins A1 (1) and B1 (4), along with related monolactyl and dilactyl esters, heterofibrins A2 (2), B2 (5), A3 (3) and B3 (6). Heterofibrin structures were assigned on the basis of detailed spectroscopic analysis, with comparison to chiral synthetic model compounds. All heterofibrins possess a diyne-ene moiety, while the monolactyl and dilactyl moiety featured in selected heterofibrins is unprecedented in the natural products literature. SAR by co-metabolite studies on the heterofibrins confirmed them to be non-cytotoxic, with the carboxylic acids 1 and 4 inhibiting lipid droplet formation in A431 fibroblast cell lines. Such inhibitors have potential application in the management of obesity, diabetes and atherosclerosis
Exploring Natural Product Artifacts: The Polyketide Enterocin Warms to a Ballet of Isomers
Publisher: American Chemical Society (ACS)
Date: 08-06-2020
Spongiaquinone Revisited: Structural and Stereochemical Studies on Marine Sesquiterpene/Quinones From a Southern Australian Marine Sponge, Spongia sp.
Publisher: CSIRO Publishing
Date: 1993
DOI: 10.1071/CH9931245
Abstract: A chemical investigation of a large purple sponge, Spongia sp., from the Great Australian Bight, resulted in the isolation of a new sesquiterpene/quinone (8), together with the known compounds dehydrocyclospongiaquinone-1 (4) and spongiaquinone (2). The last compound was also isolated as the potassium salt (9), this being the first recorded account of a naturally occurring marine sesquiterpene/quinone salt. The structure for (8) was assigned by detailed spectroscopic analysis. A re-investigation into the stereostructure of spongiaquinone (2) resulted in the first unambiguous assignment of absolute stereochemistry, and uncovered the peculiar chiroptical properties of spongiaquinone (2) and its potassium salt (9).
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.
5-epi-Isospongiaquinone, a New Sesquiterpene/Quinone Antibiotic from an Australian Marine Sponge, Spongia hispida
Publisher: American Chemical Society (ACS)
Date: 11-1992
DOI: 10.1021/NP50089A012
Abstract: An Australian marine sponge, Spongia hispida, has been found to contain a new sesquiterpene/quinone identified by detailed spectroscopic analysis and chemical derivatization as the antibiotic 5-epi-isospongiaquinone [3]. The complete stereostructure for 3 was determined by detailed spectroscopic analysis and chemical correlation with the known marine natural product isospongiaquinone [2]. Co-occurring with 3 was an ethylated analogue, 5-epi-homoisospongiaquinone [4], which was speculated to be an artifact of the isolation process. A revised structure 15 for the known marine metabolite, smenorthoquinone [13], is also presented.
Dysidealactams and Dysidealactones: Sesquiterpene Glycinyl-Lactams, Imides, and Lactones from a Dysidea sp. Marine Sponge Collected in Southern Australia
Publisher: American Chemical Society (ACS)
Date: 03-04-2020
Chemical Inhibition of Bacterial Protein Tyrosine Phosphatase Suppresses Capsule Production
Publisher: Public Library of Science (PLoS)
Date: 15-05-2012
Neochrysosporazines: Precursor-Directed Biosynthesis Defines a Marine-Derived Fungal Natural Product P-Glycoprotein Inhibitory Pharmacophore
Publisher: American Chemical Society (ACS)
Date: 22-01-2022
DOI: 10.1021/ACS.JMEDCHEM.1C01989
Abstract: Upregulation of ATP binding cassette (ABC) transporter efflux pumps (
Gymnoascolides A-C: Aromatic butenolides from an Australian isolate of the soil ascomycete Gymnoascus reessii
Publisher: American Chemical Society (ACS)
Date: 22-07-2005
DOI: 10.1021/NP050145P
Abstract: Three new aromatic butenolides, gymnoascolides A-C (1-3), have been isolated from the Australian soil ascomycete Gymnoascus reessii and assigned structures on the basis of detailed spectroscopic analysis. The absolute configurations of gymnoascolides B (2) and C (3) at C-5 were solved using a combination of chemical derivatization and quantum chemical simulations.
The effect of halide salts on the production of Gymnoascus reessii polyenylpyrroles
Publisher: American Chemical Society (ACS)
Date: 20-02-2007
DOI: 10.1021/NP0605283
Abstract: Addition of NaCl to the solid-phase fermentation of an Australian isolate of Gymnoascus reessii resulted in enhanced production of chloropolyenylpyrroles, while the addition of NaBr suppressed chloropolyenylpyrrole production in favor of bromo and dechloro analogues. Access to a wider selection of polyenylpyrroles provided scope for SAR comparisons on this rare class of cytotoxic natural products, with the bromo- and dechloropolyenylpyrroles displaying significantly reduced cytotoxicity. These results suggest that the chloro substituent is a critical element in the pharmacophore for this rare class of natural product.
Prolinimines: N-Amino-l -Pro-methyl Ester (Hydrazine) Schiff Bases from a Fish Gastrointestinal Tract-Derived Fungus, Trichoderma sp. CMB-F563
Publisher: American Chemical Society (ACS)
Date: 09-01-2018
DOI: 10.1021/ACS.ORGLETT.7B03666
Abstract: A rice cultivation of a fish gastrointestinal tract-derived fungus, Trichoderma sp. CMB-F563, yielded natural products incorporating a rare hydrazine moiety, embedded within a Schiff base. Structures inclusive of absolute configurations were assigned to prolinimines A-D (1-4) on the basis of detailed spectroscopic and C
Millmerranones A–F: A Meroterpene Cyclic Carbonate and Related Metabolites from the Australian Fungus Aspergillus sp. CMB-MRF324
Publisher: American Chemical Society (ACS)
Date: 12-10-2021
DOI: 10.1021/ACS.ORGLETT.1C03150
Abstract: A brown rice cultivation of
Antibiotics in the clinical pipeline as of December 2022
Publisher: Springer Science and Business Media LLC
Date: 08-06-2023
DOI: 10.1038/S41429-023-00629-8
Abstract: The need for new antibacterial drugs to treat the increasing global prevalence of drug-resistant bacterial infections has clearly attracted global attention, with a range of existing and upcoming funding, policy, and legislative initiatives designed to revive antibacterial R& D. It is essential to assess whether these programs are having any real-world impact and this review continues our systematic analyses that began in 2011. Direct-acting antibacterials (47), non-traditional small molecule antibacterials (5), and β-lactam/β-lactamase inhibitor combinations (10) under clinical development as of December 2022 are described, as are the three antibacterial drugs launched since 2020. Encouragingly, the increased number of early-stage clinical candidates observed in the 2019 review increased in 2022, although the number of first-time drug approvals from 2020 to 2022 was disappointingly low. It will be critical to monitor how many Phase-I and -II candidates move into Phase-III and beyond in the next few years. There was also an enhanced presence of novel antibacterial pharmacophores in early-stage trials, and at least 18 of the 26 phase-I candidates were targeted to treat Gram-negative bacteria infections. Despite the promising early-stage antibacterial pipeline, it is essential to maintain funding for antibacterial R& D and to ensure that plans to address late-stage pipeline issues succeed.
Exploiting intraspecific competitive mechanisms to control invasive cane toads (Rhinella marina)
Publisher: The Royal Society
Date: 13-06-2012
Abstract: If invasive species use chemical weapons to suppress the viability of conspecifics, we may be able to exploit those species-specific chemical cues for selective control of the invader. Cane toads ( Rhinella marina ) are spreading through tropical Australia, with negative effects on native species. The tadpoles of cane toads eliminate intraspecific competitors by locating and consuming newly laid eggs. Our laboratory trials show that tadpoles find those eggs by searching for the powerful bufadienolide toxins (especially, bufogenins) that toads use to deter predators. Using those toxins as bait, funnel-traps placed in natural waterbodies achieved near-complete eradication of cane toad tadpoles with minimal collateral damage (because most native (non-target) species are repelled by the toads' toxins). More generally, communication systems that have evolved for intraspecific conflict provide novel opportunities for invasive-species control.
The trikentrins : novel indoles from the sponge
Publisher: Elsevier BV
Date: 1986
Linear and branched polyacrylates as a delivery platform for peptide-based vaccines
Publisher: Future Science Ltd
Date: 09-2016
Abstract: Aim: Peptide-based vaccines are designed to carry the minimum required antigen to trigger the desired immune responses however, they are usually poorly immunogenic and require appropriate delivery system. Results: Peptides, B-cell epitope (J14) derived from group A streptococcus M-protein and universal T-helper (PADRE) epitope, were conjugated to a variety of linear and branched polyacrylates. All produced conjugates formed submicron-sized particles and induced a high level of IgG titres in mice after subcutaneous immunization. These polymer–peptide conjugates demonstrated high opsonization capacity against group A streptococcus clinical isolates. Conclusion: We have successfully demonstrated that submicron-sized polymer–peptide conjugates were capable of inducing strong humoral immune responses after single immunization.
Phoslactomycins Revisited: Polyketide Tetrahydrofurans and Lactones from an Australian Wasp Nest-Derived Streptomyces sp. CMB-MW079
Publisher: American Chemical Society (ACS)
Date: 06-10-2022
DOI: 10.1021/ACS.ORGLETT.2C02791
Abstract: Molecular network analysis of Streptomyces sp. CMB-MW079 detected rare phosphorylated natural products. Miniaturized cultivation profiling (MATRIX) established optimal conditions for the production, isolation, and identification of the polyketide δ-lactone phoslactomycin E ( 1 ) and new ester homologues, phoslactomycins J and K ( 2 and 3 ), as well as unprecedented heterocyclic analogues, the tetrahydrofuran cyclolactomycins A-D ( 4 - 7 ) and γ-lactone isocyclolactomycins A-C ( 8 - 10 ). We propose a biogenetic relationship linking these cometabolites with the known lactomycins A-C which were tentatively identified as minor cometabolites.
The Luffarins (A-Z), Novel Terpenes From an Australian Marine Sponge, Luffariella geometrica
Publisher: CSIRO Publishing
Date: 1992
DOI: 10.1071/CH9921705
Abstract: A marine sponge, Luffariella geometrica Kirkpatrick, collected from the southern Australian coastal waters of the Great Australian Bight, has been found to contain 14 new bicyclic sesterterpenes, luffarin-A (14), -B (15), -C (16), -D (17), -E (18), -F (19), -G (20), -H (21), -I (22), -J (23), -K (24), -L (25), -M (26) and -N (27), a new bicyclic bisnorsesterterpene, luffarin-O (30), a new monocyclic sesterterpene, luffarin-P (32), six new acyclic sesterterpenes, luffarin-Q (35), -R (36), -S (37), -T (38), -U (39) and -V (40), two new diterpenes, luffarin-W (41) and -X (44), and two new bisnorditerpenes luffarin-Y (45) and -Z (46). These novel marine metabolites have been assigned structures, including stereochemistry, on the basis of detailed spectroscopic analysis, chemical correlation, derivatization, and biosynthetic considerations. Studies directed at the absolute stereochemistry of the luffarins have also permitted assignment of absolute stereochemistry to the known marine natural products (E)-neomanoalide (3), (Z)-neomanoalide (4) and dehydroambliol-A (47).
Abyssomicins from the South China Sea Deep‐Sea Sediment Verrucosispora sp.: Natural Thioether Michael Addition Adducts as Antitubercular Prodrugs
Publisher: Wiley
Date: 06-12-2012
Genomic and Metabolomic Analysis of Antarctic Bacteria Revealed Culture and Elicitation Conditions for the Production of Antimicrobial Compounds
Publisher: MDPI AG
Date: 27-04-2020
DOI: 10.3390/BIOM10050673
Abstract: Concern about finding new antibiotics against drug-resistant pathogens is increasing every year. Antarctic bacteria have been proposed as an unexplored source of bioactive metabolites however, most biosynthetic gene clusters (BGCs) producing secondary metabolites remain silent under common culture conditions. Our work aimed to characterize elicitation conditions for the production of antibacterial secondary metabolites from 34 Antarctic bacterial strains based on MS/MS metabolomics and genome mining approaches. Bacterial strains were cultivated under different nutrient and elicitation conditions, including the addition of lipopolysaccharide (LPS), sodium nitroprusside (SNP), and coculture. Metabolomes were obtained by HPLC-QTOF-MS/MS and analyzed through molecular networking. Antibacterial activity was determined, and seven strains were selected for genome sequencing and analysis. Biosynthesis pathways were activated by all the elicitation treatments, which varies among strains and dependents of culture media. Increased antibacterial activity was observed for a few strains and addition of LPS was related with inhibition of Gram-negative pathogens. Antibiotic BGCs were found for all selected strains and the expressions of putative actinomycin, carotenoids, and bacillibactin were characterized by comparison of genomic and metabolomic data. This work established the use of promising new elicitors for bioprospection of Antarctic bacteria and highlights the importance of new “-omics” comparative approaches for drug discovery.
Chapter 12. Nuclear Magnetic Resonance Case Studies in Microbial Natural Products
Publisher: Royal Society of Chemistry
Date: 2016
Heronamycin A: a new benzothiazine ansamycin from an Australian marine-derived Streptomyces sp.
Publisher: Elsevier BV
Date: 02-2012
Shornephine A: Structure, Chemical Stability, and P-Glycoprotein Inhibitory Properties of a Rare Diketomorpholine from an Australian Marine-Derived Aspergillus sp.
Publisher: American Chemical Society (ACS)
Date: 02-09-2014
DOI: 10.1021/JO501501Z
Amaurones A–K: Polyketides from the Fish Gut-Derived Fungus Amauroascus sp. CMB-F713
Publisher: American Chemical Society (ACS)
Date: 02-02-2021
Immunogenicity Assessment of Cell Wall Carbohydrates of Group A Streptococcus via Self-Adjuvanted Glyco-lipopeptides
Publisher: American Chemical Society (ACS)
Date: 03-02-2021
Diverse Cone-Snail Species Harbor Closely Related Streptomyces Species with Conserved Chemical and Genetic Profiles, Including Polycyclic Tetramic Acid Macrolactams
Publisher: Frontiers Media SA
Date: 24-11-2017
Kinase Inhibitor Scaffolds against Neurodegenerative Diseases from a Southern Australian Ascidian, Didemnum sp.
Publisher: Wiley
Date: 24-04-2012
Abstract: Screening a library of Southern Australian and Antarctic marine invertebrates and algae for inhibitors of neurodegenerative disease kinase targets casein kinase 1 (CK1δ), cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase 3β (GSK3β) identified a Western Australian Didemnum species (CMB-02127) as a high-priority specimen. Chemical fractionation returned the known aromatic alkaloids ningalins B-D as the major metabolites, together with six minor metabolites, the new ningalins E-G and the known hexacyclic pyrrole alkaloids lamellarins Z, G and A6. All structures were assigned by detailed spectroscopic analysis and literature comparisons, and the structural assignments were supported by biosynthetic considerations. The ningalins showed potent and broad inhibition across the three kinases, while the lamellarins were generally more selective for CDK5. Docking studies using published X-ray crystal structures of CDK5 revealed both scaffolds target the ATP binding pocket.
Physical mixture of a cyclic lipopeptide vaccine induced high titres of opsonic IgG antibodies against group A streptococcus.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1BM01333E
Abstract: Untreated or reoccurring group A
Lamellarins as Inhibitors of P‐Glycoprotein‐Mediated Multidrug Resistance in a Human Colon Cancer Cell Line
Publisher: Wiley
Date: 30-03-2012
Abstract: Chemical analysis of a Didemnum sp. (CMB-01656) collected during scientific Scuba operations off Wasp Island, New South Wales, yielded five new lamellarins A1 (1), A2 (2), A3 (3), A4 (4) and A5 (5) and eight known lamellarins C (6), E (7), K (8), M (9), S (10), T (11), X (12) and χ (13). Analysis of a second Didemnum sp. (CMB-02127) collected during scientific trawling operations along the Northern Rottnest Shelf, Western Australia, yielded the new lamellarin A6 (14) and two known lamellarins G (15) and Z (16). Structures were assigned to 1-16 on the basis of detailed spectroscopic analysis with comparison to literature data and authentic s les. Access to this unique library of natural lamellarins (1-16) provided a rare opportunity for structure-activity relationship (SAR) investigations, probing interactions between lamellarins and the ABC transporter efflux pump P-glycoprotein (P-gp) with a view to reversing multidrug resistance in a human colon cancer cell line (SW620 Ad300). These SAR studies, which were expanded to include the permethylated lamellarin derivative (17) and a series of lamellarin-inspired synthetic coumarins (19-24) and isoquinolines (25-26), successfully revealed 17 as a promising new non-cytotoxic P-gp inhibitor pharmacophore.
Spiralisones A–D: acylphloroglucinol hemiketals from an Australian marine brown alga, Zonaria spiralis
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2OB26988K
Abstract: An intertidal s le of the Australian marine brown alga, Zonaria spiralis, exhibited promising kinase inhibitory and antibacterial activity. Chemical analysis returned six phloroglucinol-derived lipids, the new hemiketal spiralisones A-D (1-4) and the known chromones 5-6, and the known norsesquiterpenoid apo-9'-fucoxanthinone (7). Structures 1-7 were assigned on the basis of detailed spectroscopic analysis, biosynthetic considerations and total synthesis. Spiralisones undergo facile acid-mediated dehydration to yield the corresponding chromones, revealing for the first time that brown algal chromones may be handling artifacts rather than natural products. Hemiketals 1 and 2, and chromone 6, displayed inhibitory activity against the neurodegenerative disease kinase targets CDK5 25, CK1δ and GSK3β, while hemiketals 1, 3 and 4, and chromone 6, displayed growth inhibitory activity against the Gram-positive bacteria Bacillus subtilis (ATCC 6051 and 6633). The promising kinase inhibitory and antibacterial properties of the Z. spiralis extract were attributed to the cumulative effect of many moderately potent phloroglucinol-derived lipid co-metabolites.
New dictyodendrins as BACE inhibitors from a southern Australian marine sponge, Ianthella sp.
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2RA20322G
Fascioquinols A–F: bioactive meroterpenes from a deep-water southern Australian marine sponge, Fasciospongia sp.
Publisher: Elsevier BV
Date: 04-2011
Synchronous intramolecular cycloadditions of the polyene macrolactam polyketide heronamide C
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6CC01930G
Abstract: Two spontaneous intramolecular cycloadditions lead to the biosynthetic congeners heronamide A and B.
Cholic Acid-based Delivery System for Vaccine Candidates against Group A Streptococcus.
Publisher: American Chemical Society (ACS)
Date: 24-07-2019
Symphyocladins A–G: bromophenol adducts from a Chinese marine red alga, Symphyocladia latiuscula
Publisher: Elsevier BV
Date: 04-2012
Structure–Activity Analysis of Cyclic Multicomponent Lipopeptide Self-Adjuvanting Vaccine Candidates Presenting Group A Streptococcus Antigens
Publisher: American Chemical Society (ACS)
Date: 29-04-2020
Poly(amino acids) as a potent self-adjuvanting delivery system for peptide-based nanovaccines.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 31-01-2020
Abstract: A new vaccine immunostimulatory (adjuvant) system was developed based on fully defined polymers built from native amino acids.
Heronamides A–C, new polyketide macrolactams from an Australian marine-derived Streptomyces sp. A biosynthetic case for synchronized tandem electrocyclization
Publisher: Royal Society of Chemistry (RSC)
Date: 2010
DOI: 10.1039/C0OB00267D
Abstract: A Streptomyces sp. isolated from a shallow water sediment s le collected off Heron Island, Australia, afforded three new polyketide macrolactams, heronamides A-C (1-3). Structures were assigned to the heronamides on the basis of detailed spectroscopic analysis, chemical derivatization and biosynthetic considerations. A plausible biosynthetic pathway is proposed in which key carbocyclic ring transformations proceed via an unprecedented synchronized tandem electrocyclization. This biosynthesis provides a framework for the assignment of complete relative configurations across all heronamides, and inspires an attractive biomimetic strategy for future total syntheses. Heronamide C elicits a dramatic and reversible non-cytotoxic effect on mammalian cell morphology.
Structure-Activity Relationships of Wollamide Cyclic Hexapeptides with Activity against Drug-Resistant and Intracellular Mycobacterium tuberculosis.
Publisher: American Society for Microbiology
Date: 03-2019
DOI: 10.1128/AAC.01773-18
Abstract: Wollamides are cyclic hexapeptides, recently isolated from an Australian soil Streptomyces isolate, that exhibit promising in vitro antimycobacterial activity against Mycobacterium bovis Bacille Calmette Guérin without displaying cytotoxicity against a panel of mammalian cells. Here, we report the synthesis and antimycobacterial activity of 36 new synthetic wollamides, collated with all known synthetic and natural wollamides, to reveal structure characteristics responsible for in vitro growth-inhibitory activity against Mycobacterium tuberculosis (H37Rv, H37Ra, CDC1551, HN878, and HN353).
Aromatic Disabolenes from an Australian Marine Sponge, Arenochalina sp.
Publisher: American Chemical Society (ACS)
Date: 03-1991
DOI: 10.1021/NP50074A048
Cytochalasins from an Australian Marine Sediment-Derived Phomopsis sp (CMB-M0042F): Acid-Mediated Intramolecular Cycloadditions Enhance Chemical Diversity
Publisher: American Chemical Society (ACS)
Date: 31-08-2017
Abstract: Chemical analysis of an Australian coastal marine sediment-derived fungus, Phomopsis sp. (CMB-M0042F), yielded the known cytochalasins J (1) and H (2), together with five new analogues, cytochalasins J
Roquefortine E, a diketopiperazine from an Australian isolate of Gymnoascus reessii
Publisher: American Chemical Society (ACS)
Date: 28-10-2005
DOI: 10.1021/NP0503101
Abstract: The new isoprenylated diketopiperazine roquefortine E (6) has been isolated from an Australian soil isolate of the ascomycete Gymnoascus reessii. The known fungal metabolite roquefortine C (1) was also recovered as the major antibacterial principle, and all structures were assigned by detailed spectroscopic analysis.
Structure Revision of Penipacids A–E Reveals a Putative New Cryptic Natural Product, N-aminoanthranilic Acid, with Potential as a Transcriptional Regulator of Silent Secondary Metabolism
Publisher: MDPI AG
Date: 24-05-2022
DOI: 10.3390/MD20060339
Abstract: Reconsideration of the spectroscopic data for penipacids A–E, first reported in 2013 as the acyclic amidines 1–5 from the South China deep sea sediment-derived fungus Penicillium paneum SD-44, prompted a total synthesis structure revision as the hydrazones 6–10. This revision strongly supported the proposition that penipacids A–B (6–7) were artifact Schiff base adducts of the cryptic (undetected) natural product N-aminoanthranilic acid (11) with diacetone alcohol, induced by excessive exposure to acetone and methanol under acidic handling conditions. Likewise, the revised structures for penipacids C–D (8–9) and E (10) raise the possibility that they may also be artifact Schiff base adducts of 11 and the media constituents pyruvic acid and furfural, respectively. A review of the natural products literature revealed other Schiff base (hydrazone) natural products that might also be viewed as Schiff base adduct artifacts of 11. Having raised the prospect that 11 is an undetected and reactive cryptic natural product, we went on to establish that 11 is not cytotoxic to a range of bacterial, fungal or mammalian (human) cell types. Instead, when added as a supplement to microbial cultivations, 11 can act as a chemical cue/transcriptional regulator, activating and/or enhancing the yield of biosynthetic gene clusters encoding for other natural product chemical defenses. This study demonstrates the value of challenging the structure and artifact status of natural products, as a window into the hidden world of cryptic and highly reactive natural products.
Nocardioazines: A Novel Bridged Diketopiperazine Scaffold from a Marine-Derived Bacterium Inhibits P-Glycoprotein
Publisher: American Chemical Society (ACS)
Date: 22-04-2011
DOI: 10.1021/OL200904V
Abstract: An Australian marine sediment-derived isolate, Nocardiopsis sp. (CMB-M0232), yielded a new class of prenylated diketopiperazine, indicative of the action of a uniquely regioselective diketopiperazine indole prenyltransferase. The bridged scaffold of nocardioazine A proved to be a noncytotoxic inhibitor of the membrane protein efflux pump P-glycoprotein, reversing doxorubicin resistance in a multidrug resistant colon cancer cell.
Poly(hydrophobic amino acid)-Based Self-Adjuvanting Nanoparticles for Group A Streptococcus Vaccine Delivery
Publisher: American Chemical Society (ACS)
Date: 02-02-2021
Design and Application of In Vivo FRET Biosensors to Identify Protein Prenylation and Nanoclustering Inhibitors
Publisher: Elsevier BV
Date: 07-2012
DOI: 10.1016/J.CHEMBIOL.2012.05.019
Abstract: Protein prenylation is required for membrane anchorage of small GTPases. Correct membrane targeting is essential for their biological activity. Signal output of the prenylated proto-oncogene Ras in addition critically depends on its organization into nanoscale proteolipid assemblies of the plasma membrane, so called nanoclusters. While protein prenylation is an established drug target, only a handful of nanoclustering inhibitors are known, partially due to the lack of appropriate assays to screen for such compounds. Here, we describe three cell-based high-throughput screening amenable Förster resonance energy transfer NANOclustering and Prenylation Sensors (NANOPS) that are specific for Ras, Rho, and Rab proteins. Rab-NANOPS provides the first evidence for nanoclustering of Rab proteins. Using NANOPS in a cell-based chemical screen, we now identify macrotetrolides, known ionophoric antibiotics, as submicromolar disruptors of Ras nanoclustering and MAPK signaling.
Total Synthesis of Heronapyrrole C
Publisher: American Chemical Society (ACS)
Date: 18-12-2013
DOI: 10.1021/OL403246J
Abstract: A flexible total synthesis of the 2-nitropyrrole-derived marine natural product, (+)-heronapyrrole C, is reported. The approach is based on regioselective access to key building blocks containing the rare 4-substituted 2-nitropyrrole motif. Sharpless asymmetric epoxidation and dihydroxylation and a Shi epoxidation were used to introduce the five stereogenic centers of the bis-THF-diol side chain. The N-benzoyloxymethyl (Boz) protecting group was crucial for functionalization of the 2-nitropyrrole moiety and enabling final deprotection under mild conditions.
The Absolute Stereochemistry of Variabilin and Related Sesterterpene Tetronic Acids
Publisher: Informa UK Limited
Date: 02-1994
Chaunopyran A
Publisher: American Chemical Society (ACS)
Date: 06-04-2017
DOI: 10.1021/ACS.JNATPROD.7B00144
Abstract: Co-cultivation of Chaunopycnis sp. (CMB-MF028) and Trichoderma hamatum (CMB-MF030), fungal strains co-isolated from the inner tissue of an intertidal rock platform mollusc (Siphonaria sp), resulted in transcriptional activation of a rare class of 2-alkenyl-tetrahydropyran, chaunopyran A (7), and biotransformation and deactivation of the antifungal pyridoxatin (1), to methyl-pyridoxatin (8). This study illustrates the complexity of offensive and counter-offensive molecular defenses encountered during fungal co-cultivation, and the opportunities for activating new, otherwise transcriptionally silent secondary metabolites.
Double adjuvanting strategy for peptide-based vaccines: trimethyl chitosan nanoparticles for lipopeptide delivery
Publisher: Future Medicine Ltd
Date: 12-2016
Abstract: Aim: To develop novel polymer-based nanoscale delivery system for lipopeptide-based vaccine against group A Streptococcus (GAS). Materials & methods: Four types of lipopeptide antigen-loaded polymeric nanoparticles (NP) were prepared. NP were accessed for their capacity to be taken up by dendritic cells effect on dendritic cell maturation ability to induce mucosal and systemic immunity and capability to induce antibody responses that opsonize GAS bacteria. Results & discussion: The combination of adjuvanting properties of lipopeptides and dextran/trimethyl chitosan-based NP had a synergistic effect on humoral immunity, and the produced antibodies showed high opsonic activity against clinical GAS isolates. Conclusion: Biocompatible NP-bearing trimethyl chitosan and dextran are efficient as mucosal adjuvants for the intranasal delivery of lipopeptide-based vaccines.
EXTRAORDINARY LEVELS OF CADMIUM AND ZINC IN A MARINE SPONGE, TEDANIA-CHARCOTI TOPSENT - INORGANIC CHEMICAL DEFENSE AGENTS
Publisher: Springer Science and Business Media LLC
Date: 03-1993
DOI: 10.1007/BF01923536
Polycyclic C-deoxyaminoglycoside-polyketides from an Australian Pasture Plant Derived Streptomyces sp.
Publisher: American Chemical Society (ACS)
Date: 15-10-2021
DOI: 10.1021/ACS.ORGLETT.1C02954
Abstract: The Australian plant pasture-derived
A new lipid from an australian marine sponge, Callyspongia sp
Publisher: Wiley
Date: 06-1997
DOI: 10.1007/S11745-997-0086-0
Abstract: A specimen of the sponge Callyspongia sp. collected off the coast of New South Wales, Australia, has yielded the novel lipid (6Z, 9Z, 12Z, 15Z)-1,6,9,12,15-octadecapenten-3-one, together with (4Z, 7Z, 10Z, 13Z)-4,7,10,13-hexadecatetraenoic acid.
Development of Polyelectrolyte Complexes for the Delivery of Peptide-Based Subunit Vaccines against Group A Streptococcus.
Publisher: MDPI AG
Date: 26-04-2020
DOI: 10.3390/NANO10050823
Abstract: Peptide subunit vaccines hold great potential compared to traditional vaccines. However, peptides alone are poorly immunogenic. Therefore, it is of great importance that a vaccine delivery platform and/or adjuvant that enhances the immunogenicity of peptide antigens is developed. Here, we report the development of two different systems for the delivery of lipopeptide subunit vaccine (LCP-1) against group A streptococcus: polymer-coated liposomes and polyelectrolyte complexes (PECs). First, LCP-1-loaded and alginate/trimethyl chitosan (TMC)-coated liposomes (Lip-1) and LCP-1/alginate/TMC PECs (PEC-1) were examined for their ability to trigger required immune responses in outbred Swiss mice PEC-1 induced stronger humoral immune responses than Lip-1. To further assess the adjuvanting effect of anionic polymers in PECs, a series of PECs (PEC-1 to PEC-5) were prepared by mixing LCP-1 with different anionic polymers, namely alginate, chondroitin sulfate, dextran, hyaluronic acid, and heparin, then coated with TMC. All produced PECs had similar particle sizes (around 200 nm) and surface charges (around + 30 mV). Notably, PEC-5, which contained heparin, induced higher antigen-specific systemic IgG and mucosal IgA titers than all other PECs. PEC systems, especially when containing heparin and TMC, could function as a promising platform for peptide-based subunit vaccine delivery for intranasal administration.
Inter-Kingdom beach warfare: Microbial chemical communication activates natural chemical defences
Publisher: Springer Science and Business Media LLC
Date: 16-08-2018
Pharmacological targeting of the transcription factor SOX18 delays breast cancer in mice
Publisher: eLife Sciences Publications, Ltd
Date: 31-01-2017
DOI: 10.7554/ELIFE.21221
Abstract: Pharmacological targeting of transcription factors holds great promise for the development of new therapeutics, but strategies based on blockade of DNA binding, nuclear shuttling, or in idual protein partner recruitment have yielded limited success to date. Transcription factors typically engage in complex interaction networks, likely masking the effects of specifically inhibiting single protein-protein interactions. Here, we used a combination of genomic, proteomic and biophysical methods to discover a suite of protein-protein interactions involving the SOX18 transcription factor, a known regulator of vascular development and disease. We describe a small-molecule that is able to disrupt a discrete subset of SOX18-dependent interactions. This compound selectively suppressed SOX18 transcriptional outputs in vitro and interfered with vascular development in zebrafish larvae. In a mouse pre-clinical model of breast cancer, treatment with this inhibitor significantly improved survival by reducing tumour vascular density and metastatic spread. Our studies validate an interactome-based molecular strategy to interfere with transcription factor activity, for the development of novel disease therapeutics.
Aspergillicins A–E: five novel depsipeptides from the marine-derived fungus Aspergillus carneus
Publisher: Royal Society of Chemistry (RSC)
Date: 2003
DOI: 10.1039/B302306K
Abstract: A search for new antiparasitic agents from a strain of the fungus Aspergillus carneus isolated from an estuarine sediment collected in Tasmania, Australia, yielded the known terrestrial fungal metabolite marcfortine A (1) as an exceptionally potent antiparasitic agent. This study also yielded a series of new depsipeptides, aspergillicins A-E (2-6) and the known terrestrial fungal metabolite acyl aszonalenin (7). Marcfortine A (1) and acyl aszonalenin (7) were identified by spectroscopic analysis, with comparison to literature data. Complete stereostructures were assigned to aspergillicins A-E (2-6) on the basis of detailed spectroscopic analysis, together with ESIMS analysis of the free amino acids generated by acid hydrolysis, and HPLC analysis of Marfey derivatives prepared from the acid hydrolysate. The peptide amino acid sequence for all aspergillicins was unambiguously assigned by MS(n) ion-trap ESI mass spectrometry.
Chemical Diversity from a Chinese Marine Red Alga, Symphyocladia latiuscula
Publisher: MDPI AG
Date: 12-2017
DOI: 10.3390/MD15120374
Citrinin revisited: from monomers to dimers and beyond
Publisher: Royal Society of Chemistry (RSC)
Date: 2006
DOI: 10.1039/B600960C
Abstract: Detailed chemical analysis of the solid phase fermentation of an Australian Penicillium citrinum isolate has returned the known compounds citrinin (1), phenol A acid (6), dihydrocitrinone (7) and dihydrocitrinin (8), together with a novel cytotoxic dimer, dicitrinin A (5). Dicitrinin A (5) was determined to be a dimerised artefact of the major co-metabolite citrinin, and its structure solved by spectroscopic analysis and chemical modification. Analysis of the products encountered during the controlled decomposition of citrinin led to the discovery of additional citrinin dimers and delineated a plausible mechanistic pathway linking all monomeric and dimeric citrinin degradation products.
Blanchaquinone: A new anthraquinone from an Australian Streptomyces sp.
Publisher: American Chemical Society (ACS)
Date: 09-2004
DOI: 10.1021/NP049826V
Abstract: Chemical analysis of an Australian Streptomyces species yielded a range of known anthracyclines and biosynthetically related metabolites, including daunomycin (1), epsilon-rhodomycinone (2), 11-hydroxyauramycinone (3), 11-hydroxysulfurmycinone (4), aklavinone (5), bisanhydro-gamma-rhodomycinone (6), and the anthraquinone 7, as well as the hitherto unreported blanchaquinone (8). The structure assigned to 8 was secured by detailed spectroscopic analysis and correlation to known analogues, such as the anthraquinone 7. This account also represents the first natural occurrence of 3, 4, and 7 and the first spectroscopic characterization of 11-hydroxysulfurmycinone (4).
Chrysosporazines A–E: P-Glycoprotein Inhibitory Piperazines from an Australian Marine Fish Gastrointestinal Tract-Derived Fungus, Chrysosporium sp. CMB-F214
Publisher: American Chemical Society (ACS)
Date: 23-09-2019
DOI: 10.1021/ACS.ORGLETT.9B03094
Abstract: Chemical analysis of
Pursuing sesterterpene lactams in Australian Irciniidae sponges
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.FITOTE.2017.09.003
Abstract: Chemical investigation of two Irciniidae sponges collected by hand (SCUBA) from Australian near shore waters, afforded six new ex les of a rare class of sesterterpene lactam ircinialactams B (1), G (2), H (5), and I (6), and 8-hydroxyircinialactams C (3) and G (4) together with the new biosynthetically related lactone, ircinialactone A (7). Also isolated were seven biosynthetically related known Irciniidae metabolites ircinialactams A (8) and C (9), (7E,12E,20Z,18S)-variabilin (10), (7Z,12Z,20Z,18S)-variabilin (11), (7E,12Z,20Z,18S)-variabilin (12), (7Z,12E,20Z,18S)-variabilin (13) and irciniafuran A (14). The structure elucidation of 1-14 was achieved by detailed spectroscopic analysis, and consideration of a plausible biosynthetic relationship linking Irciniidae sesterterpene β-furans, lactams and lactones.
A New Furanoditerpene From a Southern Australian Marine Sponge, Thorectandra choanoides
Publisher: CSIRO Publishing
Date: 1995
DOI: 10.1071/CH9951903
Abstract: A specimen of the marine sponge Thorectandra choanoides from Bass Strait, Australia, has yielded the new furanoditerpene (7), the structure of which was secured by spectroscopic analysis.
Structure revision of the rare sponge metabolite echinosulfone A, and biosynthetically related echinosulfonic acids A–D
Publisher: Elsevier BV
Date: 03-2020
Bistellettazines A−C and Bistellettazole A: New Terpenyl−Pyrrolizidine and Terpenyl−Imidazole Alkaloids from a Southern Australian Marine Sponge, Stelletta sp
Publisher: American Chemical Society (ACS)
Date: 10-09-2008
DOI: 10.1021/OL8016512
Abstract: Four new alkaloids have been isolated during chemical investigations into a southern Australian marine sponge, Stelletta sp. Detailed spectroscopic analysis, supported by chemical degradation and partial synthesis, permitted structure elucidation of bistellettazines A-C ( 1- 3), the first reported ex les of terpenyl-pyrrolizidine conjugates, and bistellettazole A ( 4), a unique cyclic terpenyl-imidazole conjugate. The alkaloids 1- 4 feature unprecedented carbon skeletons that are proposed to share a common convergent biosynthetic origin, arising via the biogenic equivalent of a Diels-Alder addition between two hypothetical polyenyl norsesquiterpene precursors.
Sesquiterpenes from Laurencia SPP
Publisher: American Chemical Society (ACS)
Date: 11-1988
DOI: 10.1021/NP50060A049
Absolute Stereochemistry of Puupehenone and Related Metabolites
Publisher: American Chemical Society (ACS)
Date: 1996
DOI: 10.1021/NP9603838
Exploitation of an ant chemical alarm signal by the zodariid spiderHabronestes bradleyiWalckenaer
Publisher: The Royal Society
Date: 22-01-1996
A New Sesquiterpene Alcohol from an Antarctic sponge
Publisher: Informa UK Limited
Date: 05-1995
Microbial biotransformation as a source of chemical diversity in cane toad steroid toxins
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.BMCL.2009.01.064
Abstract: The cane toad is an invasive pest that is rapidly colonising northern Australia. The cane toad parotoid gland secretes cardiotoxic steroids (bufadienolides) that are poisoning native predator species. This study reveals bufadienolide ersity within the secretions of Australian cane toads is different to cane toads from overseas, being far more structurally erse than previously assumed. It is proposed that this variation is mediated by in situ bacterial biotransformation.
Atropselective syntheses of (−) and (+) rugulotrosin A utilizing point-to-axial chirality transfer
Publisher: Springer Science and Business Media LLC
Date: 02-02-2015
DOI: 10.1038/NCHEM.2173
Australian marine sponge alkaloids as a new class of glycine-gated chloride channel receptor modulator
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.BMC.2013.04.061
Abstract: Chemical analysis of a specimen of the sponge Ianthella cf. flabelliformis returned two new sesquiterpene glycinyl lactams, ianthellalactams A (1) and B (2), the known sponge sesquiterpene dictyodendrillin (3) and its ethanolysis artifact ethyl dictyodendrillin (4), and five known sponge indole alkaloids, aplysinopsin (5), 8E-3'-deimino-3'-oxoaplysinopsin (6), 8Z-3'-deimino-3'-oxoaplysinopsin (7), dihydroaplysinopsin (8) and tubastrindole B (9). The equilibrated mixture 6/7 exhibited glycine-gated chloride channel receptor (GlyR) antagonist activity with a bias towards α3 over α1 GlyR, while tubastrindole B (9) exhibited a bias towards α1 over α3 GlyR. At low- to sub-micromolar concentrations, 9 was also a selective potentiator of α1 GlyR, with no effect on α3 GlyR-a pharmacology that could prove useful in the treatment of movement disorders such as spasticity and hyperekplexia. Our investigations into the GlyR modulatory properties of 1-9 were further supported by the synthesis of a number of structurally related indole alkaloids.
N-Amino-l-Proline Methyl Ester from an Australian Fish Gut-Derived Fungus: Challenging the Distinction between Natural Product and Artifact
Publisher: MDPI AG
Date: 12-03-2021
DOI: 10.3390/MD19030151
Abstract: Further investigation into a fish gut-derived fungus Evlachovaea sp. CMB-F563, previously reported to produce the unprecedented Schiff base prolinimines A–B (1–2), revealed a new cryptic natural product, N-amino-l-proline methyl ester (5)—only the second reported natural occurrence of an N-amino-proline, and the first from a microbial source. To enable these investigations, we developed a highly sensitive analytical derivitization methodology, using 2,4-dinitrobenzaldehyde (2,4-DNB) to cause a rapid in situ transformation of 5 to the Schiff base 9, with the latter more readily detectable by UHPLC-DAD (400 nm) and HPLC-MS analyses. Moreover, we demonstrate that during cultivation 5 is retained in fungal mycelia, and it is only when solvent extraction disrupts mycelia that 5 is released to come in contact with the furans 7–8 (which are themselves produced by thermal transformation of carbohydrates during media autoclaving prior to fungal inoculation). Significantly, on contact, 5 undergoes a spontaneous condensation with 7–8 to yield the Schiff base prolinimines 1–2, respectively. Observations made during this study prompted us to reflect on what it is to be a natural product (i.e., 5), versus an artifact (i.e., 1–2), versus a media component (i.e., 7–8).
Parguerenes: Marine red alga bromoditerpenes as inhibitors of P-glycoprotein (ABCB1) in multidrug resistant human cancer cells
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.BCP.2013.02.005
Abstract: High intrinsic or acquired expression of membrane spanning, adenosine triphosphate binding cassette (ABC) transporter proteins, such as P-glycoprotein (P-gp), in cancers represents a major impediment to chemotherapy, with accelerated drug efflux leading to multi-drug resistance (MDR). Although ABC transporter inhibitors offer the prospect of reversing the MDR phenotype, no inhibitors have advanced to the clinic. We employed a range of intracellular fluorescence and radio-ligand accumulation and efflux assays, together with cytotoxicity and MDR reversal assays, as well as flow cytometry, fluorescence microscopy and radioimmunoprecipitation, to discover and evaluate new P-gp inhibitors from a unique library of southern Australian and Antarctic marine natural products. This study successfully characterized two rare bromoditerpenes, parguerenes I and II, sourced from a southern Australian collection of the red alga Laurencia filiformis, as P-gp inhibitors. We determined that the parguerenes were non-cytotoxic, dose-dependent inhibitors of P-gp mediated drug efflux, that modify the extracellular antibody binding epitope of P-gp in a manner that differs markedly from that of the known inhibitors verapamil and cyclosporine A. We confirmed that parguerenes were capable of reversing P-gp mediated vinblastine, doxorubicin and paclitaxel MDR, that inhibitory properties span both P-gp and multidrug resistant protein 1 (MRP1), but do not extend to breast cancer resistance protein (BCRP), and that parguerene II is superior (more potent) to verapamil. Our investigations validate the proposition that marine natural products can deliver new ABC transporter inhibitor scaffolds, with structure characteristics fundamentally different from existing inhibitor classes.
Clathrins A-C: Metabolites from a southern Australian marine sponge, Clathria species
Publisher: American Chemical Society (ACS)
Date: 27-05-2000
DOI: 10.1021/NP990644O
Abstract: A Clathria sp. collected in the Great Australian Bight has yielded the novel metabolites clathrins A (6), B (7), and C (8). Structures were assigned to clathrins A-C on the basis of spectroscopic analysis. Clathrin A (6) represents a plausible biosynthetic intermediate that provides an inferred link between marine sesquiterpene/benzenoids and mixed terpene/shikimate biosynthesis.
Lipid core peptide/poly(lactic-co-glycolic acid) as a highly potent intranasal vaccine delivery system against Group A streptococcus
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.IJPHARM.2016.09.057
Abstract: Rheumatic heart disease represents a leading cause of mortality caused by Group A Streptococcus (GAS) infections transmitted through the respiratory route. Although GAS infections can be treated with antibiotics these are often inadequate. An efficacious GAS vaccine holds more promise, with intranasal vaccination especially attractive, as it mimics the natural route of infections and should be able to induce mucosal IgA and systemic IgG immunity. Nanoparticles were prepared by either encapsulating or coating lipopeptide-based vaccine candidate (LCP-1) on the surface of poly(lactic-co-glycolic acid) (PLGA). In vitro study showed that encapsulation of LCP-1 vaccine into nanoparticles improved uptake and maturations of antigen-presenting cells. The immunogenicity of lipopeptide incorporated PLGA-based nanoparticles was compared with peptides co-administered with mucosal adjuvant cholera toxin B in mice upon intranasal administration. Higher levels of J14-specific salivary mucosal IgA and systemic antibody IgG titres were observed for groups immunized with encapsulated LCP-1 compared to LCP-1 coated nanoparticles or free LCP-1. Systemic antibodies obtained from LCP-1 encapsulated PLGA NPs inhibited the growth of bacteria in six different GAS strains. Our results show that PLGA-based lipopeptide delivery is a promising approach for rational design of a simple, effective and patient friendly intranasal GAS vaccine resulting in mucosal IgA response.
Microbiome-Mediated Biotransformation of Cane Toad Bufagenins
Publisher: American Chemical Society (ACS)
Date: 10-07-2017
DOI: 10.1021/ACS.JNATPROD.7B00134
Abstract: Cane toads are an invasive pest species in which all life stages employ cardiotoxic bufagenins as a chemical defense against predators. Curiously, the bufagenin profiles of eggs and tadpoles are more complex than those of parotoid secretion, the principle mechanism of toxin delivery in adult toads. In an effort to understand this complexity, we determined that selected strains of adult toad parotoid-gland-associated Gram-positive bacteria, Bacillus spp., were capable of biotransforming secreted bufagenins, marinobufagenin (1), telocinobufagenin (2), bufalin (3), and resibufagenin (4), to hydroxylated scaffolds commonly encountered in cane toad eggs and tadpoles. Scaled-up cultivation, preparative chromatography, and detailed spectroscopic analysis identified Bacillus sp. CMB-TD29 biotransformation products of 1, as 11α-hydroxymarinobufagenin (6), 12β-hydroxymarinobufagenin (7), and 17α-hydroxymarinobufagenin (8). Comparative bufagenin profiles across the cane toad life cycle suggest that bacterial biotransformation mediates the oxidative adaptation of adult toad bufagenins to hydroxylated bufagenins encountered in eggs and tadpoles. We speculate that knowledge of a relationship between the cane toad microbiome and bufagenin chemical defenses could inspire the development of a natural, nontoxic, environmentally sustainable bacterial biocontrol for this toxic invasive species.
Aranciamycins I and J, Antimycobacterial Anthracyclines from an Australian Marine-Derived Streptomyces sp.
Publisher: American Chemical Society (ACS)
Date: 19-03-2015
DOI: 10.1021/ACS.JNATPROD.5B00095
Abstract: Chemical analysis of an Australian marine-derived Streptomyces sp. (CMB-M0150) yielded two new anthracycline antibiotics, aranciamycins I (1) and J (2), as well as the previously reported aranciamycin A (3) and aranciamycin (4). The aranciamycins 1-4, identified by detailed spectroscopic analysis, were noncytotoxic when tested against selected Gram-negative bacteria and fungi (IC50 >30 μM) and exhibited moderate and selective cytotoxicity against Gram-positive bacteria (IC50 >1.1 μM) and a panel of human cancer cell lines (IC50 > 7.5 μM). Significantly, 1-4 were cytotoxic (IC50 0.7-1.7 μM) against the Mycobacterium tuberculosis surrogate M. bovis bacille Calmette-Guérin.
Polyglutamic acid-trimethyl chitosan-based intranasal peptide nano-vaccine induces potent immune responses against group A streptococcus
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.ACTBIO.2018.09.037
Abstract: Peptide-based vaccines have the potential to overcome the limitations of classical vaccines however, their use is h ered by a lack of carriers and adjuvants suitable for human use. In this study, an efficient self-adjuvanting peptide vaccine delivery system was developed based on the ionic interactions between cationic trimethyl chitosan (TMC) and a peptide antigen coupled with synthetically defined anionic α-poly-(l-glutamic acid) (PGA). The antigen, possessing a conserved B-cell epitope derived from the group A streptococcus (GAS) pathogen and a universal T-helper epitope, was conjugated to PGA using cycloaddition reaction. The produced anionic conjugate formed nanoparticles (NP-1) through interaction with cationic TMC. These NP-1 induced higher systemic and mucosal antibody titers compared to antigen adjuvanted with standard mucosal adjuvant cholera toxin B subunit or antigen mixed with TMC. The produced serum antibodies were also opsonic against clinically isolated GAS strains. Further, a reduction in bacterial burden was observed in nasal secretions, pharyngeal surface and nasopharyngeal-associated lymphoid tissue of mice immunized with NP-1 in GAS challenge studies. Thus, conjugation of defined-length anionic polymer to peptide antigen as a means of formulating ionic interaction-based nanoparticles with cationic polymer is a promising strategy for peptide antigen delivery. STATEMENT OF SIGNIFICANCE: A self-adjuvanting delivery system is required for peptide vaccines to enhance antigen delivery to immune cells and generate systemic and mucosal immunity. Herein, we developed a novel self-adjuvanting nanoparticulate delivery system for peptide antigens by combining polymer-conjugation and complexation strategies. We conjugated peptide antigen with anionic α-poly-(l-glutamic acid) that in turn, formed nanoparticles with cationic trimethyl chitosan by ionic interactions, without using external crosslinker. On intranasal administration to mice, these nanoparticles induced systemic and mucosal immunity, at low dose. Additionally, nanoparticles provided protection to vaccinated mice against group A streptococcus infection. Thus, this concept should be particularly useful in developing nanoparticles for the delivery of peptide antigens.
Polyethylenimine: An Intranasal Adjuvant for Liposomal Peptide-Based Subunit Vaccine against Group A Streptococcus
Publisher: American Chemical Society (ACS)
Date: 07-08-2020
Fungal Biotransformation of Tetracycline Antibiotics
Publisher: American Chemical Society (ACS)
Date: 25-07-2016
Abstract: The commercial antibiotics tetracycline (3), minocycline (4), chlortetracycline (5), oxytetracycline (6), and doxycycline (7) were biotransformed by a marine-derived fungus Paecilomyces sp. to yield seco-cyclines A-H (9-14, 18 and 19) and hemi-cyclines A-E (20-24). Structures were assigned by detailed spectroscopic analysis, and in the case of 10 X-ray crystallography. Parallel mechanisms account for substrate-product specificity, where 3-5 yield seco-cyclines and 6 and 7 yield hemi-cyclines. The susceptibility of 3-7 to fungal biotransformation is indicative of an unexpected potential for tetracycline "degradation" (i.e., antibiotic resistance) in fungal genomes. Significantly, the fungal-derived tetracycline-like viridicatumtoxins are resistant to fungal biotransformation, providing chemical insights that could inform the development of new tetracycline antibiotics resistant to enzymatic degradation.
Levoglucosenone and Its Pseudoenantiomer iso-Levoglucosenone as Scaffolds for Drug Discovery and Development
Publisher: American Chemical Society (ACS)
Date: 08-06-2020
A search for BACE inhibitors reveals new biosynthetically related pyrrolidones, furanones and pyrroles from a southern Australian marine sponge, Ianthella sp.
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2OB06747A
Abstract: Fractionation of a southern Australian marine sponge, Ianthella sp., yielded sixteen metabolites including a new class of pyrrolidone, ianthellidones A-F (1-6), a new class of furanone, ianthellidones G-H (7-8), new and known lamellarins, lamellarins O1 (9), O2 (10), O (11) and Q (12), plus the known 4-hydroxybenzaldehyde (13), 4-hydroxybenzoic acid (14), 4-methoxybenzoic acid (15) and ethyl 4-hydroxybenzoate (16). Structures for all Ianthella metabolites were determined by detailed spectroscopic analysis, supported by a plausible biosynthetic relationship. The ianthellidones were non-cytotoxic towards two human colon cancer cell lines (SW620 and SW620 Ad300), as well as Gram +ve and Gram -ve bacteria, and a fungus. Ianthellidone F (6) and lamellarins O2 (10) and O (11) displayed modest BACE inhibitory properties (IC(50) > 10 μM), while lamellarin O1 (9) was more potent (IC(50) 22 μM), was an inhibitor of the multi-drug resistance efflux pump P-glycoprotein, and displayed selective growth inhibitory activity against the Gram +ve bacterium Bacillus subtilis (ATCC 6633) (IC(50) 2.5 μM).
Glenthenamines A–F: Enamine Pyranonaphthoquinones from the Australian Pasture Plant Derived Streptomyces sp. CMB-PB042
Publisher: American Chemical Society (ACS)
Date: 24-01-2022
DOI: 10.1021/ACS.JNATPROD.1C00821
Abstract: Chemical investigations into solid phase cultivations of an Australian sheep station pasture plant derived
Glyclauxins A–E: Dimeric Oxaphenalenone Aminoglycosides from an Australian Wasp Nest-Derived Fungus Talaromyces sp. CMB-MW102
Publisher: American Chemical Society (ACS)
Date: 17-02-2023
Case Studies in Molecular Network-Guided Marine Biodiscovery
Publisher: MDPI AG
Date: 20-07-2023
DOI: 10.3390/MD21070413
Abstract: In reviewing a selection of recent case studies from our laboratory, we revealed some lessons learned and benefits accrued from the application of mass spectrometry (MS/MS) molecular networking in the field of marine sponge natural products. Molecular networking proved pivotal to our discovery of many new natural products and even new classes of natural product, some of which were opaque to alternate dereplication and prioritization strategies. Case studies included the discovery of: (i) trachycladindoles, an exceptionally rare class of bioactive indole alkaloid previously only known from a single southern Australia s le of Trachycladus laevispirulifer (ii) dysidealactams, an unprecedented class of sesquiterpene glycinyl-lactam and glycinyl-imide from a Dysidea sp., a sponge genera often discounted as having been exhaustively studied (iii) cacolides, an unprecedented family of sesterterpene α-methyl-γ-hydroxybutenolides from a Cacospongia sp., all too easily mischaracterized and deprioritized during dereplication as a well-known class of sponge sesterterpene tetronic acids and (iv) thorectandrins, a new class of indole alkaloid which revealed unexpected insights into the chemical and biological properties of the aplysinopsins, one of the earliest and more extensively reported class of sponge natural products.
Trichodermides A–E: New Peptaibols Isolated from the Australian Termite Nest-Derived Fungus Trichoderma virens CMB-TN16
Publisher: American Chemical Society (ACS)
Date: 12-03-2018
DOI: 10.1021/ACS.JNATPROD.7B01072
Abstract: Chemical analysis of a fermentation of the Australian termite nest-derived fungus Trichoderma virens CMB-TN16 yielded five new acyclic nonapeptides, trichodermides A-E (1-5). Amino acid residues, configurations, and sequences were determined by a combination of spectroscopic (NMR and MS-MS) and chemical (C
New weapons in the toad toolkit: A review of methods to control and mitigate the biodiversity impacts of invasive cane toads (rhinella marina)
Publisher: University of Chicago Press
Date: 06-2017
DOI: 10.1086/692167
Abstract: Our best hope of developing innovative methods to combat invasive species is likely to come from the study of high-profile invaders that have attracted intensive research not only into control, but also basic biology. Here we illustrate that point by reviewing current thinking about novel ways to control one of the world’s most well-studied invasions: that of the cane toad in Australia. Recently developed methods for population suppression include more effective traps based on the toad’s acoustic and pheromonal biology. New tools for containing spread include surveillance technologies (e.g., eDNA s ling and automated call detectors), as well as landscape-level barriers that exploit the toad’s vulnerability to desiccation—a strategy that could be significantly enhanced through the introduction of sedentary, range-core genotypes ahead of the invasion front. New methods to reduce the ecological impacts of toads include conditioned taste aversion in free-ranging predators, gene banking, and targeted gene flow. Lastly, recent advances in gene editing and gene drive technology hold the promise of modifying toad phenotypes in ways that may facilitate control or buffer impact. Synergies between these approaches hold great promise for novel and more effective means to combat the toad invasion and its consequent impacts on bio ersity.
Cometins (A-C), New Furanosesterterpenes From an Australian Marine Sponge, Spongia sp.
Publisher: CSIRO Publishing
Date: 1992
DOI: 10.1071/CH9921255
Abstract: The known marine furanosesterterpene furospinosulin-1 (1), together with three new furanosesterterpenes, namely cometin-A (2), cometin-B (3) and cometin-C (4), were isolated from a marine sponge, Spongia sp., collected during commercial trawling operations in the Great Australian Bight. The structures of these metabolites were determined by detailed spectroscopic analysis and chemical derivatization . The antibiotic property of the crude ethanol extract of this sponge was attributed solely to the furanosesterterpene tetronic acid cometin -A (2).
Activity Relationship of Poly(ethylenimine)-Based Liposomes as Group A Streptococcus Vaccine Delivery Systems
Publisher: American Chemical Society (ACS)
Date: 25-07-2023
Phorbasins G–K: new cytotoxic diterpenes from a southern Australian marine sponge, Phorbas sp.
Publisher: Royal Society of Chemistry (RSC)
Date: 2008
DOI: 10.1039/B808866G
Abstract: Fractionation of a cytotoxic extract obtained from a southern Australian marine sponge, Phorbas sp., yielded the known diterpenes phorbasins B-F () together with five new members of the phorbasin family, phorbasins G-K (). Structures were assigned to the new phorbasins based on detailed spectroscopic analysis. A preliminary structure activity relationship (SAR) evaluation based on the co-metabolites phorbasins B-K () revealed aspects of the phorbasin pharmacophore.
Mimicry of host cuticular hydrocarbons by salticid spider Cosmophasis bitaeniata that preys on larvae of tree ants Oecophylla smaragdina.
Publisher: Springer Science and Business Media LLC
Date: 2002
Abstract: The salticid spider Cosmophasis bitaeniata preys on the larvae of the green tree ant Oecophylla smaragdina. Gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) reveal that the cuticle of C. bitaeniata mimics the mono- and dimethylalkanes of the cuticle of its prey. Recognition bioassays with extracts of the cuticular hydrocarbons of ants and spiders revealed that foraging major workers did not respond aggressively to the extracts of the spiders or conspecific nestmates, but reacted aggressively to conspecific nonnestmates. Typically, the ants either failed to react (as with control treatments with no extracts) or they reacted nonaggressively as with conspecific nestmates. These data indicate that the qualitative chemical mimicry of ants by C. bitaeniata allows the spiders to avoid detection by major workers of O. smaragdina.
Methods in Microbial Biodiscovery
Publisher: MDPI AG
Date: 03-09-2021
DOI: 10.3390/MD19090503
Abstract: This review presents an account of the microbial biodiscovery methodology developed and applied in our laboratory at The University of Queensland, Institute for Molecular Bioscience, with ex les drawn from our experiences studying natural products produced by Australian marine-derived (and terrestrial) fungi and bacteria.
Oxandrastins: Antibacterial Meroterpenes from an Australian Mud Dauber Wasp Nest-Associated Fungus, Penicillium sp. CMB-MD14
Publisher: MDPI AG
Date: 25-11-2021
DOI: 10.3390/MOLECULES26237144
Abstract: The ethyl acetate extract of an ISP-2 agar cultivation of the wasp nest-associated fungus Penicillium sp. CMB-MD14 exhibited promising antibacterial activity against vancomycin-resistant enterococci (VRE), with a bioassay guided chemical investigation yielding the new meroterpene, oxandrastin A (1), the first andrastin-like metabolite with an extra oxygenation at C-2. A culture media optimisation strategy informed a scaled-up rice cultivation that yielded 1, together with three new oxandrastins B–D (2–4), two known andrastins C (5) and F (6), and a new meroterpene of the austalide family, isoaustalide F (7). Structures of 1–7 were assigned based on detailed spectroscopic analysis and chemical interconversion. A GNPS molecular networking analysis of the rice cultivation extract detected the known austalides B (8), H (9), and H acid (10), tentatively identified based on molecular formulae and co-clustering with 7. That the anti-VRE properties of the CMB-MD14 extract were exclusively attributed to 1 (IC50 6.0 µM, MIC99 13.9 µM), highlights the importance of the 2-OAc and 3-OAc moieties to the oxandrastin anti-VRE pharmacophore.
Lincolnenins A-D: Isomeric Bactericidal Bianthracenes from Streptomyces lincolnensis
Publisher: American Chemical Society (ACS)
Date: 15-12-2021
Polyenylpyrroles and polyenylfurans from an Australian isolate of the soil ascomycete Gymnoascus reessii
Publisher: American Chemical Society (ACS)
Date: 19-01-2006
DOI: 10.1021/OL052880Y
Abstract: [structure: see text] An Australian isolate of the soil ascomycete Gymnoascus reessii yielded a series of cytotoxic metabolites, including the known polyenylpyrroles rumbrin (1) and auxarconjugatin A (2), and the new rumbrin stereoisomer 12E-isorumbrin (3), as well as an unprecedented class of polyenylfurans exemplified by gymnoconjugatins A (4) and B (5). Structures were assigned with detailed spectroscopic analysis.
Chapter 11. Nuclear Magnetic Resonance Case Studies in Marine Natural Products
Publisher: Royal Society of Chemistry
Date: 2016
Noonindoles A–F: Rare Indole Diterpene Amino Acid Conjugates from a Marine-Derived Fungus, Aspergillus noonimiae CMB-M0339
Publisher: MDPI AG
Date: 07-11-2022
DOI: 10.3390/MD20110698
Abstract: Analytical scale chemical/cultivation profiling prioritized the Australian marine-derived fungus Aspergillus noonimiae CMB-M0339. Subsequent investigation permitted isolation of noonindoles A–F (5–10) and detection of eight minor analogues (i–viii) as new ex les of a rare class of indole diterpene (IDT) amino acid conjugate, indicative of an acyl amino acid transferase capable of incorporating a erse range of amino acid residues. Structures for 5–10 were assigned by detailed spectroscopic and X-ray crystallographic analysis. The metabolites 5–14 exhibited no antibacterial properties against G-ve and G+ve bacteria or the fungus Candida albicans, with the exception of 5 which exhibited moderate antifungal activity.
Chemical cues that attract cannibalistic cane toad (Rhinella marina) larvae to vulnerable embryos
Publisher: Springer Science and Business Media LLC
Date: 15-06-2021
DOI: 10.1038/S41598-021-90233-3
Abstract: Chemical cues produced by late-stage embryos of the cane toad ( Rhinella marina ) attract older conspecific larvae, which are highly cannibalistic and can consume an entire clutch. To clarify the molecular basis of this attraction response, we presented captive tadpoles with components present in toad eggs. As previously reported, attractivity arises from the distinctive toxins (bufadienolides) produced by cane toads, with some toxins (e.g., bufagenins) much stronger attractants than others (e.g., bufotoxins). Extracts of frozen toad parotoid glands (rich in bufagenins) were more attractive than were fresh MeOH extracts of the parotoid secretion (rich in bufotoxins), and purified marinobufagin was more effective than marinobufotoxin. Cardenolide aglycones (e.g., digitoxigenin) were active attractors, whereas C-3 glycosides (e.g., digoxin, oubain) were far less effective. A structure–activity relationship study revealed that tadpole attractant potency strongly correlated with Na + /K + ATPase inhibitory activity, suggesting that tadpoles monitor and rapidly react to perturbations to Na + /K + ATPase activity.
The Development of Surface-Modified Liposomes as an Intranasal Delivery System for Group A Streptococcus Vaccines
Publisher: MDPI AG
Date: 30-01-2023
Abstract: Intranasal vaccine administration can overcome the disadvantages of injectable vaccines and present greater efficiency for mass immunization. However, the development of intranasal vaccines is challenged by poor mucosal immunogenicity of antigens and the limited availability of mucosal adjuvants. Here, we examined a number of self-adjuvanting liposomal systems for intranasal delivery of lipopeptide vaccine against group A Streptococcus (GAS). Among them, two liposome formulations bearing lipidated cell-penetrating peptide KALA and a new lipidated chitosan derivative (oleoyl-quaternized chitosan, OTMC) stimulated high systemic antibody titers in outbred mice. The antibodies were fully functional and were able to kill GAS bacteria. Importantly, OTMC was far more effective at stimulating antibody production than the classical immune-stimulating trimethyl chitosan formulation. In a simple physical mixture, OTMC also enhanced the immune responses of the tested vaccine, without the need for a liposome delivery system. The adjuvanting capacity of OTMC was further confirmed by its ability to stimulate cytokine production by dendritic cells. Thus, we discovered a new immune stimulant with promising properties for mucosal vaccine development.
Isolation and synthesis of N-acyladenine and adenosine alkaloids from a southern Australian marine sponge, Phoriospongia sp.
Publisher: Elsevier BV
Date: 10-2014
Chrysosporazines Revisited: Regioisomeric Phenylpropanoid Piperazine P-Glycoprotein Inhibitors from Australian Marine Fish-Derived Fungi
Publisher: MDPI AG
Date: 16-05-2022
DOI: 10.3390/MOLECULES27103172
Abstract: A library of fungi previously recovered from the gastrointestinal tract (GIT) of several fresh, commercially sourced Australian mullet fish was re-profiled for production of a rare class of phenylpropanoid piperazine alkaloids (chrysosporazines) using an integrated platform of (i) miniaturized 24-well plate cultivation profiling (MATRIX), (ii) UPLC-DAD and UPLC-QTOF-MS/MS (GNPS) chemical profiling, and (iii) precursor directed biosynthesis to manipulate in situ biosynthetic performance and outputs to detect two new fungal producers of chrysosporazines. Chemical analysis of an optimized PDA solid phase cultivation of Aspergillus sp. CMB-F661 yielded the new regioisomeric chrysosporazine T (1) and U (2), while precursor directed cultivation lified production and yielded the very minor new natural products azachrysosporazine T1 (3) and U1 (4), and the new unnatural analogues neochrysosporazine R (5) and S (6). Likewise, chemical analysis of an optimized M1 solid phase cultivation of Spiromastix sp. CMB-F455 lead to the GNPS detection of multiple chrysosporazines and brasiliamides, and the isolation and structure elucidation of chrysosporazine D (7) and brasiliamide A (8). Access to new chrysosporazine regioisomers facilitated structure activity relationship investigations to better define the chrysosporazine P-glycoprotein (P-gp) inhibitory pharmacophore, which is exceptionally potent at reversing doxorubrin resistance in P-gp over expressing colon carcinoma cells (SW600 Ad300).
Nocardiopsins C and D and nocardiopyrone A: new polyketides from an Australian marine-derived Nocardiopsis sp.
Publisher: Elsevier BV
Date: 2013
Bromocatechol conjugates from a Chinese marine red alga, Symphyocladia latiuscula
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.PHYTOCHEM.2018.10.026
Abstract: This study describes an investigation into polybromocatechol conjugates isolated from a marine red alga, Symphyocladia latiuscula (Harvey) Yamada, collected from coastal waters off Qingdao, China. We report on the isolation and characterisation of eight undescribed aconitic acid conjugates, symphyocladins R-X, including a likely solvolysis artifact of symphyocladin S, and an undescribed furanoyl conjugate, symphyocladin Y. Structure elucidation was achieved by detailed spectroscopic analysis. A plausible biosynthetic pathway linking all these co-metabolites through a cascade of quinone methide additions is proposed.
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.
Heronapyrrole D: A case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery
Publisher: Beilstein Institut
Date: 26-05-2014
DOI: 10.3762/BJOC.10.121
Abstract: The heronapyrroles A–C have first been isolated from a marine-derived Streptomyces sp. (CMB-0423) in 2010. Structurally, these natural products feature an unusual nitropyrrole system to which a partially oxidized farnesyl chain is attached. The varying degree of oxidation of the sesquiterpenyl subunit in heronapyrroles A–C provoked the hypothesis that there might exist other hitherto unidentified metabolites. On biosynthetic grounds a mono-tetrahydrofuran-diol named heronapyrrole D appeared a possible candidate. We here describe a short asymmetric synthesis of heronapyrrole D, its detection in cultivations of CMB-0423 and finally the evaluation of its antibacterial activity. We thus demonstrate that biosynthetic considerations and the joint effort of synthetic and natural product chemists can result in the identification of new members of a rare class of natural products.
Self-assembling lipopeptides with a potent activity against Gram-positive bacteria, including multidrug resistant strains
Publisher: Future Medicine Ltd
Date: 11-2015
DOI: 10.2217/NNM.15.137
Abstract: Aim: To explore the potential of de novo designed cyclic lipopeptides and its linear counterparts as antibacterial agents. Materials & methods: The lipopeptides were synthesized via solid-phase peptide synthesis and the cyclization was achieved by using succinic acid linker. The antimicrobial activities of the lipopeptides were evaluated in vitro against a variety selection of Gram-negative and Gram-positive bacteria including clinical isolates of multidrug-resistant strains. Results: The synthesized lipopeptides were able to self-assemble into nanoparticles in an aqueous environment, with three exhibiting potent antibacterial activity against Gram-positive bacteria, including clinically relevant multidrug-resistant bacteria. Conclusion: The lead compounds have the potential to be developed as new antibacterials that are effective against Gram-positive bacteria, including multidrug-resistant isolates.
Small-Molecule Inhibitors of the SOX18 Transcription Factor
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.CHEMBIOL.2017.01.003
Abstract: Pharmacological modulation of transcription factors (TFs) has only met little success over the past four decades. This is mostly due to standard drug discovery approaches centered on blocking protein/DNA binding or interfering with post-translational modifications. Recent advances in the field of TF biology have revealed a central role of protein-protein interaction in their mode of action. In an attempt to modulate the activity of SOX18 TF, a known regulator of vascular growth in development and disease, we screened a marine extract library for potential small-molecule inhibitors. We identified two compounds, which inspired a series of synthetic SOX18 inhibitors, able to interfere with the SOX18 HMG DNA-binding domain, and to disrupt HMG-dependent protein-protein interaction with RBPJ. These compounds also perturbed SOX18 transcriptional activity in a cell-based reporter gene system. This approach may prove useful in developing a new class of anti-angiogenic compounds based on the inhibition of TF activity.
New PKS-NRPS tetramic acids and pyridinone from an Australian marine-derived fungus, Chaunopycnis sp.
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5OB01058F
Abstract: Marine-derived fungus Chaunopycnis sp. yielded the tetramic acid F-14329 ( 1 ) and new analogues, chaunolidines A–C ( 2–4 ), together with the new pyridinone chaunolidone A ( 5 ), and pyridoxatin ( 6 ).
Poly(hydrophobic Amino Acids) and Liposomes for Delivery of Vaccine against Group A Streptococcus
Publisher: MDPI AG
Date: 29-07-2022
Abstract: Adjuvants and delivery systems are essential components of vaccines to increase immunogenicity against target antigens, particularly for peptide epitopes (poor immunogens). Emulsions, nanoparticles, and liposomes are commonly used as a delivery system for peptide-based vaccines. A Poly(hydrophobic amino acids) delivery system was previously conjugated to Group A Streptococcus (GAS)-derived peptide epitopes, allowing the conjugates to self-assemble into nanoparticles with self adjuvanting ability. Their hydrophobic amino acid tail also serves as an anchoring moiety for the peptide epitope, enabling it to be integrated into the liposome bilayer, to further boost the immunological responses. Polyleucine-based conjugates were anchored to cationic liposomes using the film hydration method and administered to mice subcutaneously. The polyleucine-peptide conjugate, its liposomal formulation, and simple liposomal encapsulation of GAS peptide epitope induced mucosal (saliva IgG) and systemic (serum IgG, IgG1 and IgG2c) immunity in mice. Polyleucine acted as a potent liposome anchoring portion, which stimulated the production of highly opsonic antibodies. The absence of polyleucine in the liposomal formulation (encapsulated GAS peptide) induced high levels of antibody titers, but with poor opsonic ability against GAS bacteria. However, the liposomal formulation of the conjugated vaccine was no more effective than conjugates alone self-assembled into nanoparticles.
Brevianamides with Antitubercular Potential from a Marine-Derived Isolate of Aspergillus versicolor
Publisher: American Chemical Society (ACS)
Date: 10-09-2012
DOI: 10.1021/OL302051X
Abstract: An Aspergillus versicolor isolated from sediment collected from the Bohai Sea, China, yielded the new dimeric diketopiperazine brevianamide S (1), together with three new monomeric cometabolites, brevianamides T (2), U (3), and V (4). Structures were determined by detailed spectroscopic analysis. Brevianamide S exhibited selective antibacterial activity against Bacille Calmette-Guérin (BCG), suggestive of a new mechanism of action that could inform the development of next-generation antitubercular drugs.
Does Osmotic Stress Affect Natural Product Expression in Fungi?
Publisher: MDPI AG
Date: 13-02-2017
DOI: 10.3390/MD15080254
AMPK and endothelial nitric oxide synthase signaling regulates KRas plasma membrane interactions via cyclic GMP-dependent protein kinase 2
Publisher: Informa UK Limited
Date: 12-2016
DOI: 10.1128/MCB.00365-16
Natural products as anthelmintics: safeguarding animal health
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D3NP00019B
Abstract: All natural products reported to December 2022 active against helminths (nematodes, tapeworms and flukes) that infect livestock and companion animals.
Amycolatopsins A–C: antimycobacterial glycosylated polyketide macrolides from the Australian soil Amycolatopsis sp. MST-108494
Publisher: Springer Science and Business Media LLC
Date: 25-10-2017
DOI: 10.1038/JA.2017.119
Abstract: A southern Australian soil isolate, Amycolatopsis sp. MST-108494, was subjected to a panel of fermentation and media optimization trials, supported by analytical chemical profiling, to detect and enhance production of a rare class of secondary metabolites. Chemical fractionation of two complementary fermentations yielded three new polyketides, identified by detailed spectroscopic analysis as the glycosylated macrolactones, amycolatopsins A (1), B (2) and C (3), closely related to the ammocidins and apoptolidins. Amycolatopsins 1 and 3 selectively inhibited growth of Mycobacterium bovis (BCG) and Mycobacterium tuberculosis (H37Rv) when compared with other Gram-positive or Gram-negative bacteria, with 3 exhibiting low levels of cytotoxicity toward mammalian cells. Thus, our data reveal promising structure activity relationship correlations where the antimycobacterial properties of amycolatopsins are enhanced by hydroxylation of the 6-Me (that is, 1 and 3), whereas mammalian cytotoxicity is decreased by hydrolysis of the disaccharide moiety (that is, 3).
Cytotoxic Spiroepoxide Lactone and Its Putative Biosynthetic Precursor from Goniobranchus Splendidus
Publisher: American Chemical Society (ACS)
Date: 15-06-2017
Lamellarins Q and R: New Aromatic Metabolites From an Australian Marine Sponge, Dendrilla cactos
Publisher: CSIRO Publishing
Date: 1995
DOI: 10.1071/CH9951491
Abstract: A specimen of Dendrilla cactos collected off the coast of New South Wales, Australia, has yielded two new alkaloids, lamellarins Q (19) and R (20), the structures of which were secured by spectroscopic analysis and by chemical derivatization.
Lipopolysaccharide (LPS) stimulation of fungal secondary metabolism
Publisher: Informa UK Limited
Date: 03-07-2014
Structural and stereochemical investigations into bromotyrosine-derived metabolites from southern Australian marine sponges, Pseudoceratina spp.
Publisher: Elsevier BV
Date: 11-2012
Divirensols: Sesquiterpene Dimers from the Australian Termite Nest-Derived Fungus Trichoderma virens CMB-TN16
Publisher: American Chemical Society (ACS)
Date: 31-12-2018
DOI: 10.1021/ACS.JNATPROD.8B00746
Abstract: A chemical investigation of the Australian termite nest-derived fungus Trichoderma virens CMB-TN16 yielded the known sesquiterpene gliocladic acid (1), together with two new acetylated analogues, 3-acetylgliocladic acid (2) and 14-acetylgliocladic acid (3), and seven new dimeric congeners, irensols A-G (4-10). All metabolites were identified by detailed spectroscopic analysis, supported by biosynthetic considerations, and were assessed for antibacterial and cytotoxic properties. The irensols are ex les of an exceptionally rare class of dimeric sesquiterpene, likely linked via a highly convergent biosynthetic pathway. HPLC-DAD-MS analysis of the crude fungal extract detected ions attributed to putative monomeric biosynthetic precursors.
Diindolylmethane Derivatives: New Selective Blockers for T-Type Calcium Channels
Publisher: MDPI AG
Date: 30-07-2022
DOI: 10.3390/MEMBRANES12080749
Abstract: The natural product indole-3-carbinol (I3C) and its major digestive product 3,3′-diindolylmethane (DIM) have shown clinical promise in multiple forms of cancer including breast cancer. In this study, we explored the calcium channel activity of DIM, its synthetic derivative 3,3′-Diindolylmethanone (DIM-one) and related I3C and DIM-one analogs. For the first time, DIM, DIM-one and analog IX were identified as selective blockers for T-type CaV3.3 (IC50s DIM 2.09 µM DIM-one 9.07 µM) while compound IX inhibited both CaV3.2 (6.68 µM) and CaV3.3 (IC50 = 3.05 µM) using a FLIPR cell-based assay to measure inhibition of T-type calcium channel window current. Further characterization of DIM by electrophysiology revealed it inhibited inward Ca2+ current through CaV3.1 (IC50 = 8.32 µM) and CaV3.3 (IC50 = 9.63 µM), while IX partially blocked CaV3.2 and CaV3.3 inward Ca2+ current. In contrast, DIM-one preferentially blocked CaV3.1 inward Ca2+ current (IC50 = 1.53 µM). The anti-proliferative activities of these compounds revealed that oxidation of the methylene group of DIM shifted the selectivity of DIMs from breast cancer cell line MCF-7 to colon cancer cell line HT-29.
Naseseazines A and B: A New Dimeric Diketopiperazine Framework from a Marine-Derived Actinomycete, Streptomyces sp.
Publisher: American Chemical Society (ACS)
Date: 05-08-2009
DOI: 10.1021/OL901466R
Abstract: Chemical analysis of a Streptomyces sp. (CMB-MQ030) isolated from a Fijian marine sediment yielded two new diketopiperazines, naseseazines A and B (1, 2), featuring a new dimeric framework. Structures were determined by detailed spectroscopic analysis and C(3) Marfey's analysis.
Precursor-Directed Biosynthesis Mediated Amplification of Minor Aza Phenylpropanoid Piperazines in an Australian Marine Fish-Gut-Derived Fungus, Chrysosporium sp. CMB-F214
Publisher: MDPI AG
Date: 25-08-2021
DOI: 10.3390/MD19090478
Abstract: Chemical analysis of an M1 agar plate cultivation of a marine fish-gut-derived fungus, Chrysosporium sp. CMB-F214, revealed the known chrysosporazines A–D (11–14) in addition to a suite of very minor aza analogues 1–6. A microbioreactor (MATRIX) cultivation profiling analysis failed to deliver cultivation conditions that significantly improved the yields of 1–6 however, it did reveal that M2 agar cultivation produced the new natural product 15. A precursor-directed biosynthesis strategy adopting supplementation of a CMB-F214 M1 solid agar culture with sodium nicotinate enhanced production of otherwise inaccessible azachrysposorazines A1 (1), A2 (2), B1 (3), C1 (4), C2 (5) and D1 (6), in addition to four new chrysosporazines chrysosporazines N–P (7–9) and spirochrysosporazine A (10). Structures inclusive of absolute configurations were assigned to 1–15 based on detailed spectroscopic and chemical analyses, and biosynthetic considerations. Non-cytotoxic to human carcinoma cells, azachrysosporazies 1–5 were capable of reversing doxorubicin resistance in P-glycoprotein (P-gp)-overexpressing human colon carcinoma cells (SW620 Ad300), with optimum activity exhibited by the C-2′ substituted analogues 3–5.
Mirabilin G: A new alkaloid from a southern Australian marine sponge, Clathria species
Publisher: American Chemical Society (ACS)
Date: 24-04-2001
DOI: 10.1021/NP000564G
Abstract: A Clathria sp. collected during scientific trawling operations in the Great Australian Bight, Australia, has yielded the new alkaloid mirabilin G (1). A structure was secured for 1 by detailed spectroscopic analysis and comparison to known marine alkaloids.
High-Throughput Screening of Australian Marine Organism Extracts for Bioactive Molecules Affecting the Cellular Storage of Neutral Lipids
Publisher: Public Library of Science (PLoS)
Date: 08-08-2011
Reveromycins Revealed: New polyketidespiroketals from Australian marine-derived and terrestrial Streptomyces spp. A case of natural productsvs. artifacts
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C0OB00654H
Abstract: Chemical analysis of fermentation products from two Australian Streptomyces isolates yielded all four known and twelve new ex les of the rare reveromycin class of polyketide spiroketals, including hemi-succinates, hemi-fumarates and hemi-furanoates. Reveromycins were identified with the aid of HPLC-DAD-MS and HPLC-DAD-SPE-NMR methodology, and structures were assigned by detailed spectroscopic analysis. The structural and mechanistic requirements for an unprecedented hemi-succinate : ketal-succinyl equilibrium were defined and provided a basis for proposing that reveromycin 4'-methyl esters and 5,6-spiroketals were artifacts. A plausible reveromycin polyketide biosynthesis is proposed, requiring a 2-methylsuccinyl-CoA starter unit, with flexible incorporation of a C(6-8) polyketide chain extension and diacid esterification units. Structure activity relationship investigations by co-metabolites were used to assess the anticancer, antibacterial and antifungal properties of reveromycins.
Quinolactacins revisited: from lactams to imide and beyond
Publisher: Royal Society of Chemistry (RSC)
Date: 2006
DOI: 10.1039/B600959J
Abstract: Chemical analysis of a solid phase fermentation of an Australian Penicillium citrinum strain has returned all known ex les of a rare class of N-methyl quinolone lactams, quinolactacins A2 (1), B2 (2), C2 (3) and A1 (4), together with the new quinolactacins B1 (5), C1 (6), D1 (7) and D2 (8), and the novel derivatives quinolonimide (9) and quinolonic acid (10). Complete stereostructures were assigned to all these compounds by detailed spectroscopic analysis and chemical interconversion. Carefully controlled and monitored decomposition studies have confirmed that quinolactacins readily undergo C-3 epimerization and oxidation, and under appropriate conditions convert to quinolonimide and quinolonic acid. Mechanisms for key transformations are proposed. The decomposition studies suggested that only quinolactacins A2 (1) and B2 (2) are genuine natural products, with all other isolated compounds being decomposition artefacts. Quinolactacins C1 (6), C2 (3), and the racemic mixture of quinolactacins D1/D2 (8/7) all displayed notable cytotoxic activity.
Choose Your Weaponry: Selective Storage of a Single Toxic Compound, Latrunculin A, by Closely Related Nudibranch Molluscs
Publisher: Public Library of Science (PLoS)
Date: 20-01-2016
Polyacrylate-Peptide Antigen Conjugate as a Single-Dose Oral Vaccine against Group A Streptococcus.
Publisher: MDPI AG
Date: 13-01-2020
Abstract: Group A Streptococcus (GAS)-associated rheumatic heart disease is a leading cause of death caused by GAS infection. While antibiotics can treat the infection in most cases, growing antibiotic resistance, late medical intervention, and recurrent infection are major obstacles to the effective treatment of GAS-associated diseases. As GAS infection typically originates from the bacterial colonization of mucosal tissue in the throat, an oral vaccine that can generate both systemic and mucosal immune responses would solve problems associated with traditional medical interventions. Moreover, orally delivered vaccines are more easily administered and less expensive for mass immunization. In this study, the B-cell epitope J8, derived from GAS M protein, and universal T-helper Pan HLA-DR-binding epitope peptide (PADRE), were conjugated to poly (methyl acrylate) (PMA) to form a self-assembled nanoparticle vaccine candidate (PMA-P-J8). Strong systemic and mucosal immune responses were induced upon single oral immunization of mice with the conjugate. The antibodies generated were opsonic against GAS clinical isolates as measured after boost immunization. Thus, we developed a simple conjugate as an effective, adjuvant-free oral peptide-based vaccine.
Talaropeptides A-D: Structure and Biosynthesis of Extensively N-methylated Linear Peptides From an Australian Marine Tunicate-Derived Talaromyces sp.
Publisher: Frontiers Media SA
Date: 04-09-2018
Long‐term quantification of the release of monomers from dental resin composites and a resin‐modified glass ionomer cement
Publisher: Wiley
Date: 2002
DOI: 10.1002/JBM.10184
Abstract: This study quantified the release of monomers from polymerized specimens of four commercially available resin composites and one glass ionomer cement immersed in water:ethanol solutions. In idual standard curves were prepared from five monomers: (1) triethylene glycol dimethacrylate (TEGDMA), (2) 2-hydroxy-ethyl methacrylate (HEMA), (3) urethane dimethacrylate (UDMA), (4) bisphenol A glycidyl dimethacrylate (BISGMA), and (5) bisphenol A. The concentration of the monomers was determined at Days 1, 7, 30, and 90 with the use of electrospray ionization/mass spectrometry. Data were expressed in mean micromol per mm(2) surface area of specimen and analyzed with Scheffe's test (p<0.05). The following monomers were found in water: monomers (1) and (2) from Delton sealant, monomer (5) from ScotchBond Multipurpose Adhesive and Delton sealant, monomer (3) from Definite and monomer (4) from Fuji II LC, ScotchBond Multipurpose Adhesive, Synergy and Definite. All these monomers increased in concentration over time, with the exception of monomer (1) from Delton sealant. Monomers (3) and (5) were found in extracts of materials despite their absence from the manufacturer's published composition. All monomers were released in significantly higher concentrations in water:ethanol solutions than in water. The greatest release of monomers occurred in the first day. The effect of the measured concentrations of monomers (1-5) on human genes, cells, or tissues needs to be considered with the use of a biological model.
Synthesis of Pseudellone Analogs and Characterization as Novel T-type Calcium Channel Blockers
Publisher: MDPI AG
Date: 28-11-2018
DOI: 10.3390/MD16120475
Abstract: T-type calcium channel (CaV3.x) blockers are receiving increasing attention as potential therapeutics for the treatment of pathophysiological disorders and diseases, including absence epilepsy, Parkinson’s disease (PD), hypertension, cardiovascular diseases, cancers, and pain. However, few clinically approved CaV3.x blockers are available, and selective pharmacological tools are needed to further unravel the roles of in idual CaV3.x subtypes. In this work, through an efficient synthetic route to the marine fungal product pseudellone C, we obtained bisindole alkaloid analogs of pseudellone C with a modified tryptophan moiety and identified two CaV3.2 (2, IC50 = 18.24 µM 3, IC50 = 6.59 µM) and CaV3.3 (2, IC50 = 7.71 µM 3, IC50 = 3.81 µM) selective blockers using a FLIPR cell-based assay measuring CaV3.x window currents. Further characterization by whole-cell patch-cl revealed a preferential block of CaV3.1 activated current (2, IC50 = 5.60 µM 3, IC50 = 9.91 µM), suggesting their state-dependent block is subtype specific.
Mollemycin A: an antimalarial and antibacterial glyco-hexadepsipeptide-polyketide from an Australian marine-derived Streptomyces sp. (CMB-M0244).
Publisher: American Chemical Society (ACS)
Date: 11-03-2014
DOI: 10.1021/OL5003913
Abstract: A marine-derived Streptomyces sp. (CMB-M0244) isolated from a sediment collected off South Molle Island, Queensland, produced mollemycin A (1) as a new first in class glyco-hexadepsipeptide-polyketide. The structure of 1 was assigned by detailed spectroscopic analysis, supported by chemical derivatization and degradation, and C3 Marfey's analysis. Mollemycin A (1) exhibits exceptionally potent and selective growth inhibitory activity against Gram-positive and Gram-negative bacteria (IC50 10-50 nM) and drug-sensitive (3D7 IC50 7 nM) and multidrug-resistant (Dd2 IC50 9 nM) clones of the malaria parasite Plasmodium falciparum.
9-(5'-Deoxy-5'-thio-β-D-xylofuranosyl)adenine Disulfide from the Southern Australian Marine Sponge Trachycladus laevispirulifer: the First Natural Occurrence of a Nucleoside Disulfide
Publisher: CSIRO Publishing
Date: 2010
DOI: 10.1071/CH09645
Abstract: Chemical fractionation of a southern Australian marine sponge, Trachycladus laevispirulifer, yielded 9-(5′-deoxy-5′-thio-β-d-xylofuranosyl)adenine disulfide as the first recorded natural occurrence of a nucleoside disulfide, and only the second of a xylo-nucleoside. Structure elucidation of the disulfide was achieved by detailed spectroscopic analysis and comparison to synthetic model compounds. The antibacterial, antifungal, and anticancer properties of the disulfide are documented and the literature surrounding natural and synthetic thionucleosides is reviewed.
Neobulgarones Revisited: Anti and Syn Bianthrones from an Australian Mud Dauber Wasp Nest-Associated Fungus, Penicillium sp. CMB-MD22
Publisher: American Chemical Society (ACS)
Date: 03-02-2021
DOI: 10.1021/ACS.JNATPROD.0C01035
Abstract: We report on the chemical analysis of a mud dauber wasp nest-associated fungus,
Polyphenylalanine as a self-adjuvanting delivery system for peptide-based vaccines: the role of peptide conformation
Publisher: CSIRO Publishing
Date: 08-12-2022
DOI: 10.1071/CH22167
Abstract: Peptide-based vaccines are composed of minimal microbial components that are required to stimulate immune responses. Peptide antigens are easy to produce, relatively cheap and non-toxic. They are also able to activate the immune system in a well-controlled manner. However, peptides themselves are poor immunogens and have to be co-administered with an adjuvant (immune stimulator) to produce desired immune responses. Unfortunately, many adjuvants are toxic, poorly effective or not compatible with peptide antigens. Recently, we demonstrated that, upon conjugation to a peptide antigen, poly(hydrophobic amino acids) can self-assemble into nanoparticles and induce strong humoral immune responses. Here, we examine the ability of polyphenylalanine to act as a self-adjuvanting moiety when conjugated to a peptide antigen derived from Group A Streptococcus M-protein. The polyphenylalanine moiety was further lipidated to alter the conjugate conformation and its ability to form nanoparticles. The lipidated analogue triggered the production of a high level of antibodies in immunized mice. The antibodies produced were highly opsonic against tested GAS clinical isolates.
Structure-activity relationship of group A streptococcus lipopeptide vaccine candidates in trimethyl chitosan-based self-adjuvanting delivery system
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.EJMECH.2019.06.047
Abstract: Synthetic peptide vaccines based on epitopes derived from the conserved region of M-protein are proving to be a realistic option for protection against group A streptococcus (GAS). However, peptide epitopes alone are poorly immunogenic due to lack of pathogen-associated structural patterns. Therefore, we developed a GAS peptide vaccine based on combined lipidic TLR 2 agonist and self-adjuvanting polymers. We synthesized three α-poly-l-glutamic acid (PGA) conjugated lipopeptides composed of 2-amino-d,l-hexadecanoic acid, GAS B-cell peptide epitope J8 (QAEDKVKQSREAKKQVEKALKQLEDKVQ) and universal T-helper epitope PADRE (AKFVAAWTLKAAA) in different spatial arrangements. The anionic lipopeptide conjugates formed nanoparticles via ionic-complexation with a cationic polymer, trimethyl chitosan (TMC). We demonstrated that the spatial arrangement of vaccine components has a significant influence on peptide conformation and particle formation and, as such, contributes to the differential efficacy and opsonin-mediated killing potential of nanovaccines. Nanoparticles carrying branched helical lipopeptide with T-helper epitope on free N-termini (NP3) stimulated the most potent humoral immune responses. Lipopeptides without TMC (LP1-LP3) and TMC nanoparticles of peptide alone (without lipid) NP (P1) were poor inducers of antibody production, indicating that both TMC and lipid are required to induce a strong opsonic immune response.
Cyanogenic polymorphism in Eucalyptus polyanthemos Schauer subsp. vestita L. Johnson and K. Hill (Myrtaceae)
Publisher: Elsevier BV
Date: 07-2002
Cottoquinazoline A and Cotteslosins A and B, Metabolites from an Australian Marine-Derived Strain of Aspergillus versicolor
Publisher: American Chemical Society (ACS)
Date: 26-02-2009
DOI: 10.1021/NP800777F
Abstract: An Australian marine-derived isolate of Aspergillus versicolor (MST-MF495) yielded the known fungal metabolites sterigmatocystin, violaceol I, violaceol II, diorcinol, (-)-cyclopenol, and viridicatol, along with a new alkaloid, cottoquinazoline A (1), and two new cyclopentapeptides, cotteslosins A (2) and B (3). Structures for 1-3 and the known compounds were determined by spectroscopic analysis. The absolute configurations of 1-3 were addressed by chemical degradation and application of the C(3) Marfey's method. The use of "cellophane raft" high-nutrient media as a device for up-regulating secondary metabolite ersity in marine-derived fungi is discussed. The antibacterial properties displayed by A. versicolor (MST-MF495) were attributed to the phenols violaceol I, violaceol II, and diorcinol, while cotteslosins 2 and 3 were identified as weak cytotoxic agents.
Alarm cues experienced by cane toad tadpoles affect post-metamorphic morphology and chemical defences
Publisher: Wiley
Date: 16-01-2009
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