Heterocyclic cellular lipid peroxidation inhibitors inspired by the marine antioxidant barettin

Accepted manuscript version. Published version available at https://doi.org/10.1016/j.bioorg.2018.11.024. Licensed CC BY-NC-ND 4.0.The marine environment remains a rich source for the discovery and development of novel bioactive compounds. The present paper describes the design, synthesis and biological evaluation of a library of small molecule heterocyclic mimetics of the marine 2,5-diketopiperazine barettin which is a powerful natural antioxidant. By mainly focusing on the influence from the brominated indole and heterocyclic core of barettin, a library of 19 compounds was prepared. The compounds comprised a heterocyclic core, either a 2,5 diketopiperazine, an imidazolidinedione or a thioxothiazolidinone, which were mainly monosubstituted with ranging bulky substituents. The prepared compounds were screened for activity in a cellular lipid peroxidation assay using HepG2 cells. Several of the synthetic compounds showed antioxidant properties superior to the positive control barettin. Two of the prepared compounds displayed inhibitory activity similar to commercial antioxidants with significant inhibition at low µg/mL concentrations. The toxicity of the compounds was also investigated against MRC-5 lung fibroblasts and none of the included compounds displayed any toxicity at 50 µg/mL

The bromotyrosine derivative Ianthelline isolated from the Arctic marine sponge Stryphnus fortis inhibits marine micro- and macrobiofouling

International audienceThe inhibition of marine biofouling by the bromotyrosine derivative ianthelline, isolated from the Arctic marine sponge Stryphnus fortis, is described. All major stages of the fouling process are investigated. The effect of ianthelline on adhesion and growth of marine bacteria and microalgae is tested to investigate its influence on the initial microfouling process comparing with the known marine antifoulant barettin as a reference. Macrofouling is studied via barnacle (Balanus improvisus) settlement assays and blue mussel (Mytilus edulis) phenoloxidase inhibition. Ianthelline is shown to inhibit both marine micro-and macrofoulers with a pronounced effect on marine bacteria (minimum inhibitory concentration (MIC) values 0.1-10 mu g/mL) and barnacle larval settlement (IC50= 3.0 mu g/mL). Moderate effects are recorded on M. edulis (IC50= 45.2 mu g/mL) and microalgae, where growth is more affected than surface adhesion. The effect of ianthelline is also investigated against human pathogenic bacteria. Ianthelline displayed low micromolar MIC values against several bacterial strains, both Gram positive and Gram negative, down to 2.5 mu g/mL. In summary, the effect of ianthelline on 20 different representative marine antifouling organisms and seven human pathogenic bacterial strains is presented

Bioassay-guided fractionation leads to the detection of cholic acid generated by the rare thalassomonas sp.

Bacterial symbionts of marine invertebrates are rich sources of novel, pharmaceutically relevant natural products that could become leads in combatting multidrug-resistant pathogens and treating disease. In this study, the bioactive potential of the marine invertebrate symbiont Thalassomonas actiniarum was investigated. Bioactivity screening of the strain revealed Gram-positive specific antibacterial activity as well as cytotoxic activity against a human melanoma cell line (A2058). The dereplication of the active fraction using HPLC-MS led to the isolation and structural elucidation of cholic acid and 3-oxo cholic acid. T. actiniarum is one of three type species belonging to the genus Thalassomonas. The ability to generate cholic acid was assessed for all three species using thin-layer chromatography and was confirmed by LC-MS. The re-sequencing of all three Thalassomonas type species using long-read Oxford Nanopore Technology (ONT) and Illumina data produced complete genomes, enabling the bioinformatic assessment of the ability of the strains to produce cholic acid. Although a complete biosynthetic pathway for cholic acid synthesis in this genus could not be determined based on sequence-based homology searches, the identification of putative penicillin or homoserine lactone acylases in all three species suggests a mechanism for the hydrolysis of conjugated bile acids present in the growth medium, resulting in the generation of cholic acid and 3-oxo cholic acid. With little known currently about the bioactivities of this genus, this study serves as the foundation for future investigations into their bioactive potential as well as the potential ecological role of bile acid transformation, sterol modification and quorum quenching by Thalassomonas sp. in the marine environmen

Discovery and biosynthetic investigation of a new antibacterial dehydrated non‐ribosomal tripeptide

Acknowledgement: QF and HD are grateful to the University of Aberdeen Elphinstone Scholarship and Scottish Funding Council/ScotCHEM (PEER/PERCE) for financial support. HD, ZL and SW thank the financial supports of Biotechnology and Biological Sciences Research Council UK (BBSRC, BB/P00380X/1) and the Royal Society-NSFC Newton Mobility Grant Award (IEC\NSFC\170617 to HD). HD, SAM and CP thank Business Interaction Vouchers (BIV009) from BBSRC funded Natural Products discovery and bioengineering Network (NPRONET). Y.G. thanks NSFC oversea scholarship, Natural Science Foundation of Jiangsu Province (BK20170450), and the Open Research fund of Jiangsu Key Laboratory of Marine Biotechnology (HS2017003).Peer reviewedPostprin

Signalling and Bioactive Metabolites from Streptomyces sp. RK44

Q.F. is grateful to the University of Aberdeen Elphinstone Scholarship and Scottish Funding Council/ScotCHEM for financial support through the PEER/PERCE Funding. FM thanks the University of the Philippines for the Faculty, Reps and Staff Development Program (FRAS DP) for the PhD grant fellowship. HD and KK thank the financial supports of Leverhulme Trust-Royal Society Africa award (AA090088) and the jointly funded UK Medical Research Council-UK Department for International Development (MRC/DFID) Concordat agreement African Research Leaders Award (MR/S00520X/1).Peer reviewedPublisher PD

Four new suomilides isolated from the cyanobacterium Nostoc sp. KVJ20 and proposal of their biosynthetic origin

The suomilide and the banyasides are highly modified and functionalized non-ribosomal peptides produced by cyanobacteria of the order Nostocales. These compound classes share several substructures, including a complex azabicyclononane core, which was previously assumed to be derived from the amino acid tyrosine. In our study we were able to isolate and determine the structures of four suomilides, named suomilide B – E (1–4). The compounds differ from the previously isolated suomilide A by the functionalization of the glycosyl group. Compounds 1–4 were assayed for anti-proliferative, anti-biofilm and anti-bacterial activities, but no significant activity was detected. The sequenced genome of the producer organism Nostoc sp. KVJ20 enabled us to propose a biosynthetic gene cluster for suomilides. Our findings indicated that the azabicyclononane core of the suomilides is derived from prephenate and is most likely incorporated by a proline specific non-ribosomal peptide synthetase-unit

Probing the therapeutic potential of marine phyla by spe extraction

The marine environment is potentially a prolific source of small molecules with significant biological activities. In recent years, the development of new chromatographic phases and the progress in cell and molecular techniques have facilitated the search for marine natural products (MNPs) as novel pharmacophores and enhanced the success rate in the selection of new potential drug candidates. However, most of this exploration has so far been driven by anticancer research and has been limited to a reduced number of taxonomic groups. In this article, we report a test study on the screening potential of an in-house library of natural small molecules composed of 285 samples derived from 57 marine organisms that were chosen from among the major eukaryotic phyla so far represented in studies on bioactive MNPs. Both the extracts and SPE fractions of these organisms were simultaneously submitted to three different bioassays—two phenotypic and one enzymatic—for cytotoxic, antidiabetic, and antibacterial activity. On the whole, the screening of the MNP library selected 11 potential hits, but the distribution of the biological results showed that SPE fractionation increased the positive score regardless of the taxonomic group. In many cases, activity could be detected only in the enriched fractions after the elimination of the bulky effect due to salts. On a statistical basis, sponges and molluscs were confirmed to be the most significant source of cytotoxic and antimicrobial products, but other phyla were found to be effective with the other therapeutic target