This review covers the literature published between January and December in 2018 for marine natural products (MNPs), with 717 citations (706 for the period January to December 2018) referring to ...compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1554 in 469 papers for 2018), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that led to the revision of structures or stereochemistries, have been included. The proportion of MNPs assigned absolute configuration over the last decade is also surveyed.
Marine natural products Blunt, John W; Carroll, Anthony R; Copp, Brent R ...
Natural product reports,
01/2018, Letnik:
35, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Covering: 2016. Previous review: Nat. Prod. Rep., 2017, 34, 235-294This review covers the literature published in 2016 for marine natural products (MNPs), with 757 citations (643 for the period ...January to December 2016) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1277 in 432 papers for 2016), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that led to the revision of structures or stereochemistries, have been included.
Covering: January to December 2017This review covers the literature published in 2017 for marine natural products (MNPs), with 740 citations (723 for the period January to December 2017) referring to ...compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1490 in 477 papers for 2017), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that led to the revision of structures or stereochemistries, have been included. Geographic distributions of MNPs at a phylogenetic level are reported.
A diverse range of strategies leading to natural product derived or inspired screening libraries aims to increase the number of new chemical entities emerging per year. However, the use of isolated ...natural products as scaffolds for the semi-synthesis of larger biological screening libraries remains rare. This particular method avoids the time-consuming and resource intensive de novo synthetic strategy for scaffold production, and has become more feasible through improvements to synthetic and isolation methodologies. This Highlight examines the increasing popularity of small- to large-sized screening libraries generated directly from isolated natural products. Several of the examples detailed herein show how this strategy can lead to improvements in not only potency but also other important (and often forgotten) drug discovery parameters such as toxicity, selectivity, lipophilicity and bioavailability. However, there are still improvements to be made to this method, particularly in the choice of the natural product scaffold and the derivatising reagents used. Avoidance of known nuisance compounds or structural alert motifs (e.g. PAINS) that interfere with bioactivity screens, and impact downstream drug development will play a significant role in the future success of this methodology. Incorporation of rational design strategies that take into account the physicochemical parameters (e.g. log P, MW, HBA, HBD) of the final semi-synthetic library analogues will also facilitate the discovery and development of leads and drugs. A multi-pronged approach to drug discovery that incorporates the use of isolated natural product scaffolds for library generation will surely be beneficial.
Weak cell-surface adhesion of cell lines to tissue culture surfaces is a common problem and presents technical limitations to the design of experiments. To overcome this problem, various surface ...coating protocols have been developed. However, a comparative and precise real-time measurement of their impact on cell behavior has not been conducted. The prostate cancer cell line LNCaP, derived from a patient lymph node metastasis, is a commonly used model system in prostate cancer research. However, the cells' characteristically weak attachment to the surface of tissue culture vessels and cover slips has impeded their manipulation and analysis and use in high throughput screening. To improve the adherence of LNCaP cells to the culture surface, we compared different coating reagents (poly-L-lysine, poly-L-ornithine, collagen type IV, fibronectin, and laminin) and culturing conditions and analyzed their impact on cell proliferation, adhesion, morphology, mobility and gene expression using real-time technologies. The results showed that fibronectin, poly-L-lysine and poly-L-ornithine improved LNCaP cells adherence and provoked cell morphology alterations, such as increase of nuclear and cellular area. These coating reagents also induced a higher expression of F-actin and reduced cell mobility. In contrast, laminin and collagen type IV did not improve adherence but promoted cell aggregation and affected cell morphology. Cells cultured in the presence of laminin displayed higher mobility than control cells. All the coating conditions significantly affected cell viability; however, they did not affect the expression of androgen receptor-regulated genes. Our comparative findings provide important insight for the selection of the ideal coating reagent and culture conditions for the cancer cell lines with respect to their effect on proliferation rate, attachment, morphology, migration, transcriptional response and cellular cytoskeleton arrangement.
Covering: January to December 2021This review covers the literature published in 2021 for marine natural products (MNPs), with 736 citations (724 for the period January to December 2021) referring to ...compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1425 in 416 papers for 2021), together with the relevant biological activities, source organisms and country of origin. Pertinent reviews, biosynthetic studies, first syntheses, and syntheses that led to the revision of structures or stereochemistries, have been included. An analysis of the number of authors, their affiliations, domestic and international collection locations, focus of MNP studies, citation metrics and journal choices is discussed.
Covering: 1877 to 2017The ancestors of present-day crinoids are thought to be some of the earliest echinoderms, with fossil records dating back to the early Paleozoic Era (Ordovician Period, 505-440 ...million years ago). Their bright colours have been noted for over 100 years, and are attributed to a series of polyketide-derived pigments. Some crinoid metabolites display a range of biological activities, including cytotoxicity and fish anti-feedant activity. This review is divided into two parts. Part 1 is encyclopedic in scope, collating information on the >50 known metabolites isolated from crinoids, including their taxonomic source, collection location, chemical structure and biological activities. During the compilation of this data, two distinct themes emerged. Firstly, there is little variation in the class of metabolites produced by crinoids, irrespective of their species or geographic origin. Secondly, the complete and unambiguous assignment of crinoid metabolite structures has been, in many cases, a difficult task. This has been due to a lack of spectroscopic technology available in the past, the presence of proton-poor chemical structures, or both. Thus, Part 2 provides a critical discussion of crinoid chemistry, including the biosynthetic origin of crinoid pigments, as well as the pitfalls and solutions experienced by ourselves and other chemists when elucidating the chemical structures of crinoid metabolites.
Kinetoplastid parasites cause vector-borne parasitic diseases including leishmaniasis, human African trypanosomiasis (HAT) and Chagas disease. These Neglected Tropical Diseases (NTDs) impact on some ...of the world's lowest socioeconomic communities. Current treatments for these diseases cause severe toxicity and have limited efficacy, highlighting the need to identify new treatments. In this study, the Davis open access natural product-based library was screened against kinetoplastids (
DD8,
and
) using phenotypic assays. The aim of this study was to identify hit compounds, with a focus on improved efficacy, selectivity and potential to target several kinetoplastid parasites. The IC
values of the natural products were obtained for
DD8,
and
in addition to cytotoxicity against the mammalian cell lines, HEK-293, 3T3 and THP-1 cell lines were determined to ascertain parasite selectivity. Thirty-one compounds were identified with IC
values of ≤ 10 µM against the kinetoplastid parasites tested. Lissoclinotoxin E (
) was the only compound identified with activity across all three investigated parasites, exhibiting IC
values < 5 µM. In this study, natural products with the potential to be new chemical starting points for drug discovery efforts for kinetoplastid diseases were identified.
Tuberculosis remains a significant global health pandemic. There is an urgent need for new anti-tubercular agents to combat the rising incidence of drug resistance and to offer effective and additive ...therapeutic options. High-throughput screening of a subset of the NatureBank marine fraction library (n = 2000) identified a sample derived from an Australian marine sponge belonging to the order Haplosclerida that displayed promising anti-mycobacterial activity. Bioassay-guided fractionation of the organic extract from this Haplosclerida sponge led to the purification of previously identified antimicrobial pyrrole alkaloids, axinellamines A (1) and B (2). The axinellamine compounds were found to have a 90% minimum inhibitory concentration (MIC90) of 18 µM and 15 µM, respectively. The removal of protein and complex carbon sources reduced the MIC90 of 1 and 2 to 0.6 and 0.8 µM, respectively. The axinellamines were not toxic to mammalian cells at 25 µM and significantly reduced the intracellular bacterial load by >5-fold. These data demonstrate that axinellamines A and B are effective anti-tubercular agents and promising targets for future medicinal chemistry efforts.
While natural products or their derivatives and mimics have contributed around 50% of current drugs, there has been no approach allowing front-loading of chemical space compliant with lead- and ...drug-like properties. The importance of physicochemical properties of molecules in the development of orally bioavailable drugs has been recognized. Classical natural product drug discovery has only been able to undertake this analysis retrospectively after compounds are isolated and structures elucidated. The present approach addresses front-loading of both extracts and subsequent fractions with desired physicochemical properties prior to screening for drug discovery. The physicochemical profiles of natural products active against two neglected disease targets, malaria and African trypanosomiasis, are presented based on this strategy. This approach can ensure timely development of natural product leads at a hitherto unachievable rate.
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