Brominated Polyacetylenic Acids from the Marine Sponge Xestospongia muta: Inhibitors of HIV Protease

Patil, Ashok D.; Kokke, W. C. M. C.; Cochran, S. Patricia; Francis, Terry; Tomszek, Thaddeus; Westley, John

doi:10.1021/np50087a002

Cited by 90 publications

(72 citation statements)

References 8 publications

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“…The diacetylene-containing fatty acid 35G has been co-isolated with the structurally related trans-enyne 35A [368]. A later study found a series of brominated fatty acids with acetylenic groups at the 5, 7, 13, 15, and 17 positions (35D, 35H-K, 35N-O) [370]. In contrast to plant lipids, these brominated natural products contained exclusively trans-alkenes.…”

Section: Marine Fatty Acids Andmentioning

confidence: 99%

Biosynthesis and function of polyacetylenes and allied natural products

Minto

Blacklock

2008

Progress in Lipid Research

290

228

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Polyacetylenic natural products are a substantial class of often unstable compounds containing a unique carbon-carbon triple bond functionality, that are intriguing for their wide variety of biochemical and ecological functions, economic potential, and surprising mode of biosynthesis. Isotopic tracer experiments between 1960 and 1990 demonstrated that the majority of these compounds are derived from fatty acid and polyketide precursors. During the past decade, research into the metabolism of polyacetylenes has swiftly advanced, driven by the cloning of the first genes responsible for polyacetylene biosynthesis in plants, moss, fungi, and actinomycetes, and the initial characterization of the gene products.The current state of knowledge of the biochemistry and molecular genetics of polyacetylenic secondary metabolic pathways will be presented together with an up-to-date survey of new terrestrial and marine natural products, their known biological activities, and a discussion of their likely metabolic origins.

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Section: Marine Fatty Acids Andmentioning

confidence: 99%

Biosynthesis and function of polyacetylenes and allied natural products

Minto

Blacklock

2008

Progress in Lipid Research

290

228

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“…Many natural products from marine organisms are currently under investigation for cancer and pain treatments (Newman and Cragg, 2004), but they are also of interest for their potential as novel anti-viral therapies (Gustafson et al, 2004). Numerous compounds derived from marine organisms have been shown to exhibit anti-HIV activity through targeting a variety of essential HIV-specific enzymes, including the viral protease (Patil et al, 1992). Hence, it was of interest to us to screen our marine extracts for SARS-CoV 3CL pro inhibitory activity.…”

Section: Discussionmentioning

confidence: 99%

Development of a red-shifted fluorescence-based assay for SARS-coronavirus 3CL protease: identification of a novel class of anti-SARS agents from the tropical marine sponge Axinella corrugata

Hamill

Hudson

Kao³

et al. 2006

Biological Chemistry

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SARS-coronavirus (SARS-CoV) encodes a main protease, 3CLpro, which plays an essential role in the viral life cycle and is currently the prime target for discovering new anti-coronavirus agents. In this article, we report our success in developing a novel red-shifted (RS) fluorescence-based assay for 3CLpro and its application for identifying small-molecule anti-SARS agents from marine organisms. We have synthesised and characterised the first generation of a red-shifted internally quenched fluorogenic substrate (RS-IQFS) for 3CLpro based on resonance energy transfer between the donor and acceptor pair CAL Fluor Red 610 and Black Hole Quencher-1 (Km and kcat values of 14 microM and 0.65 min-1). The RS-IQFS primary sequence was selected based on the results of our screening analysis of 3CLpro performed using a series of blue-shifted (BS)-IQFSs corresponding to the 3CLpro-mediated cleavage junctions of the SARS-CoV polyproteins. In contrast to BS-IQFSs, the RS-IQFS was not susceptible to fluorescence interference from coloured samples and allowed for successful screening of marine natural products and identification of a coumarin derivative, esculetin-4-carboxylic acid ethyl ester, a novel 3CLpro inhibitor (IC50=46 microM) and anti-SARS agent (EC50=112 microM; median toxic concentration>800 microM) from the tropical marine sponge Axinella corrugata.

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“…L'acide 14,16-dibromohexadéca-7E,13E,15Z-trièn-5-ynoïque a été isolé d'une Xestospongia australienne (Schmitz et Gorichand, 1978). Les AG bromés des éponges Xestospongia et leurs esters ont une activité antibactérienne significative (Bourguet-Kondracki et al, 1992) et inhibent l'action de l'enzyme protéase jouant un rôle crucial dans la réplication du virus d'immunodéficience humaine (Patil et al, 1992). Les éponges des familles Nepheliospongia et Haploscleria produisent aussi des métabolites et des AG acétyléniques (Cimino et al, 1985).…”

Section: Ag Bromésunclassified

Acides gras inhabituels des organismes marins : une illustration de la biodiversité moléculaire marine

Barnathan

2010

OCL

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In addition to the common polyunsaturated fatty acids (FA) such as those of the n-3 and n-6 series with major interest in health and nutrition, marine organisms (invertebrates and algae) produce unique FA including branched, methoxylated, halogenated, acetylenic and non-methylene-interrupted structures. The biosynthetic pathways, and the structural and functional roles of these uncommon FA are often not yet known. This short overview wishes to be an outline on the particular FA classes possessing uncommon structures, especially those of increasing interest regarding their promising biological activities.

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Brominated Polyacetylenic Acids from the Marine Sponge Xestospongia muta: Inhibitors of HIV Protease

Cited by 90 publications

References 8 publications

Biosynthesis and function of polyacetylenes and allied natural products

Biosynthesis and function of polyacetylenes and allied natural products

Development of a red-shifted fluorescence-based assay for SARS-coronavirus 3CL protease: identification of a novel class of anti-SARS agents from the tropical marine sponge Axinella corrugata

Acides gras inhabituels des organismes marins : une illustration de la biodiversité moléculaire marine

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