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Pesticides are a major contaminant in coastal waters and can cause adverse effects in marine invertebrates such as jellyfish. Most studies have investigated short‐term responses of organisms to unrealistically high concentrations of pesticides; however, chronic exposure to persistent low concentrations, which are more likely to occur in the environment, are rarely analyzed. We tested the response of polyps of the moon jellyfish Aurelia aurita to environmental concentrations of the herbicide atrazine and the insecticide chlorpyrifos, individually and in combination, over 9 wk. We hypothesized that exposure to individual pesticides would reduce rates of asexual reproduction and alter polyps' metabolite profiles, and that the results would be more severe when polyps were exposed to the combined pesticides. Polyps survived and reproduced (through budding) in all treatments, and no differences among treatments were observed. Proton nuclear magnetic resonance spectroscopy revealed no difference in profiles of polar metabolites of polyps exposed to the individual or combined pesticides. Our results suggest that A. aurita polyps are unaffected by chronic exposure to atrazine and chlorpyrifos at concentrations recommended as being protective by current Australian water quality guidelines. Environ Toxicol Chem 2020;39:1685–1692. © 2020 SETAC [ABSTRACT FROM AUTHOR]

The heparan sulfate mimetic PI-88 is a complex mixture of sulfated oligosaccharides with anti-metastatic and anti-angiogenic activity due to its potent inhibition of heparanase and heparan sulfate-dependent angiogenic growth factors. It was recently in Phase III clinical trials for postresection hepatocellular carcinoma. The major oligosaccharide constituents of PI-88 were prepared for the first time by sulfonation of individually purified phosphorylated oligosaccharides isolated from the PI-88 precursor. PI-88 and its components were subjected to detailed 1D and 2D NMR spectroscopic analysis. The spectra of the individual components greatly assisted the assignment of minor resonances in the 1H NMR spectrum of PI-88. The data also showed that the majority of the oligosaccharides in PI-88 are fully sulfated and that undersulfated species present are largely due to anomeric desulfation. The solution conformation of the phosphomannopentaose sulfate (major component) of PI-88 was then determined by a combination of molecular dynamics simulations and NOE measurements which may provide insights into its binding interactions with target proteins. [ABSTRACT FROM AUTHOR]

Abstract: Isoprenylcysteine methyltransferase (Icmt) catalyzes the carboxyl methylation of oncogenic proteins in the final step of a series of post-translational modifications. The inhibition of Icmt provides an attractive and novel anticancer target. A natural product high-throughput screening campaign was conducted to discover inhibitors of Icmt. The Australian marine sponge, Pseudoceratina sp., yielded spermatinamine, a novel alkaloid with a bromotyrosyl-spermine-bromotyrosyl sequence, as the bioactive constituent. Its structure was determined by 1D and 2D NMR spectroscopy. Spermatinamine is the first natural product inhibitor of Icmt. [Copyright &y& Elsevier]

Two novel indolizidine alkaloids, grandisine A (1) and B (2), and the known alkaloid (-) isoelaeocarpiline (3) were isolated from the leaves of Elaeocarpus grandis and their structures determined by 1D and 2D NMR spectroscopy. The compounds showed affinity for the human δ-opioid receptor. Grandisine A contains a unique tetracyclic skeleton, while grandisine B possesses the unique combination of isoquinuclidinone and indolizidine groups in one molecule. [ABSTRACT FROM AUTHOR]

Abstract: A new tribrominated indole alkaloid, kororamide A together with the known alkaloid convolutamine F, were isolated through the application of mass directed purification from the bryozoan, Amathia tortuosa collected from northern New South Wales, Australia. The structure of kororamide A was deduced from the analysis of 1D/2D NMR and MS data. Kororamide A exists in solution as a mixture of interconverting cis–trans amide regioisomers in a ratio of 4:5. Bioactivity testing demonstrated that kororamide A was marginally active against chloroquine-sensitive and resistant strains of the malarial parasite Plasmodium falciparum, and was inactive against normal human cell lines. [Copyright &y& Elsevier]

Abstract: A new natural product, lysianadioic acid, was isolated from the plant Lysiana subfalcata as a carboxypeptidase B (CPB) inhibitor. It is a potent inhibitor of CPB with an IC50 of 0.36μM. This is the first known example of a small molecule CPB inhibitor isolated from plant origin. Its structure was determined by NMR spectroscopy. [Copyright &y& Elsevier]

Abstract The phytochemical investigation of the leaf extract of Uvaria cherrevensis (Annonaceae) yielded three new cyclohexene (9 Z)-octadec-9-enyl ethers, cherrevenols M-O (1 – 3), and a known fatty ester derivative (4). The structures of the isolated compounds were elucidated by spectroscopic and computer-aided molecular modelling methods. Ozone Induced Dissociation (OzID) mass spectrometry was employed to determine the C-9 position of the side chain olefinic double bonds, while 13C NMR spectroscopy indicated their (Z)-configurations. All isolated compounds were evaluated for their antimalarial and cytotoxic activities; all were inactive. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Organic carrier solvents are used in aquatic toxicity testing to improve chemical solubility and facilitate the exploration of dose-response relationships. Both water- and solvent-control groups are normally included in these scenarios to ensure that the solvent itself has no effect on the test organism, but this fails to consider possible interactive effects between carrier solvents and contaminants of interest. We explored this topic by exposing Limnodynastes peronii tadpoles to a mixture of common water-soluble pharmaceuticals (diclofenac, metformin and valproic acid) in the presence and absence of the carrier solvent methanol, according to standard developmental bioassay methodology. Nuclear Magnetic Resonance (NMR) spectroscopy was applied as a platform for untargeted metabolomics, to compare broad sub-lethal hepatotoxicity in solvent- and solvent-free exposure scenarios. Considerable interactive effects were identified between the pharmaceutical mixture and a typical dose of methanol (0.003%). Specifically, pronounced differences were observed between the solvent- and solvent-free exposure groups for leucine, acetate, glutamine, citrate, glycogen, tyrosine, arginine, purine nucleotides and an unidentified metabolite at 6.53 ppm. Various other metabolites exhibited similar disparity related to the use of carrier solvent, but the interactions were non-significant. These results raise important questions about the use of carrier solvents for chemical exposures in aquatic ecotoxicology, and particularly for studies interested in sub-lethal mechanistic information and/or biomarker discovery. [ABSTRACT FROM AUTHOR]

Four tropane alkaloids, including a new compound triuniamine A ( 3 ) a known compound 2,3-dihydrodarlingine ( 4 ) with previously unassigned relative configuration and two known compounds darlingine ( 1 ), 10-hydroxydarlingine ( 2 ) were obtained from the stems of the endemic Australian plant Triunia montana (Proteaceae). The structure and relative configuration of the stereogenic centers in triuniamine A was elucidated on the basis of 1D and 2D NMR spectroscopy and high-resolution mass spectrometry. The relative configuration of the four stereogenic centers in 2,3-dihydrodarlingine were established from ROESY correlations, and its absolute configuration assigned from comparison of its ECD spectrum with that of (+)-darlingine. [ABSTRACT FROM AUTHOR]

Two phloroglucinols named tomentosones A and B (1 and 2) that each possess a novel hexacyclic ring system were isolated from the CH2C2 extract of Rhodomyrtus tomentosa leaves. Their structures were elucidated from analyses of 2D NMR spectroscopic data. Tomentosone A inhibited the growth of chloroquine-resistant and -sensitive strains of the malaria parasite Plasmodium falciparum, with IC50 values of 1.49 µM and 1.0 µM, respectively, while tomentosone B was significantly less active. [ABSTRACT FROM AUTHOR]

Abstract: Bioassay-guided fractionation of the crude CH2Cl2/MeOH extract from the Australian ascidian Polysyncraton echinatum led to the isolation of a new pyridoacridine alkaloid, 12-deoxyascididemin (1), along with two known analogues, ascididemin (2) and eilatin (3). The structure of 1 was determined following extensive analysis of 1D/2D NMR and MS data. Biological evaluation showed that compounds 1–3 are potent antitrypanosomal agents with IC50 values of 0.077, 0.032, and 1.33μM against Trypanosoma brucei brucei, respectively. [Copyright &y& Elsevier]