Bistramides A, B, C, D, and K: A New Class of Bioactive Cyclic Polyethers from Lissoclinum bistratum

Biard, Jean-François; Roussakis, Christos; Kornprobst, Jean Michel; Gouiffes-Barbin, Danielle; Verbist, Jean-François; Cotelle, Philippe; Foster, Mark P.; Ireland, Chris M.; Debitus, Cécile

doi:10.1021/np50112a002

Cited by 77 publications

(79 citation statements)

References 5 publications

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“…TB1. The extract of L. bistratum also contained major metabolites, including the bistramides and the bistratamides group of compounds (Degnan et al, 1989;Biard et al, 1994;Perez and Faulkner, 2003). However, in most samples, especially those from California, the majority of the components could not be assigned from databases, such as Antimarin and the Dictionary of Natural Products.…”

Section: Bioactivity Profile Of Ascidian Chemical Extractsmentioning

confidence: 99%

Species specificity of symbiosis and secondary metabolism in ascidians

et al. 2014

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Ascidians contain abundant, diverse secondary metabolites, which are thought to serve a defensive role and which have been applied to drug discovery. It is known that bacteria in symbiosis with ascidians produce several of these metabolites, but very little is known about factors governing these 'chemical symbioses'. To examine this phenomenon across a wide geographical and species scale, we performed bacterial and chemical analyses of 32 different ascidians, mostly from the didemnid family from Florida, Southern California and a broad expanse of the tropical Pacific Ocean. Bacterial diversity analysis showed that ascidian microbiomes are highly diverse, and this diversity does not correlate with geographical location or latitude. Within a subset of species, ascidian microbiomes are also stable over time (R ¼ À 0.037, P-value ¼ 0.499). Ascidian microbiomes and metabolomes contain species-specific and location-specific components. Location-specific bacteria are found in low abundance in the ascidians and mostly represent strains that are widespread. Location-specific metabolites consist largely of lipids, which may reflect differences in water temperature. By contrast, species-specific bacteria are mostly abundant sequenced components of the microbiomes and include secondary metabolite producers as major components. Species-specific chemicals are dominated by secondary metabolites. Together with previous analyses that focused on single ascidian species or symbiont type, these results reveal fundamental properties of secondary metabolic symbiosis. Different ascidian species have established associations with many different bacterial symbionts, including those known to produce toxic chemicals. This implies a strong selection for this property and the independent origin of secondary metabolite-based associations in different ascidian species. The analysis here streamlines the connection of secondary metabolite to producing bacterium, enabling further biological and biotechnological studies.

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Section: Bioactivity Profile Of Ascidian Chemical Extractsmentioning

confidence: 99%

Species specificity of symbiosis and secondary metabolism in ascidians

et al. 2014

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“…Its ring and tail moieties together are essentially the structural equivalent for half of the dimeric cyclic lactone of swinholide A [46]. (vii) Finally, bistramides are a unique family of dilactam polyethers isolated from the marine ascidian Lissoclinum bistratum that have recently been shown to target actin with high affinity and inhibit filament formation and promote filament disruption [47][48][49]. Interest- ingly, there is virtually no structural similarity between bistramides and other known G-actin-binding toxins.…”

Section: Barbed End-targeting Compoundsmentioning

confidence: 99%

Actin-targeting natural products: structures, properties and mechanisms of action

Allingham

Klenchin

Rayment

2006

Cell. Mol. Life Sci.

189

168

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Natural small-molecule inhibitors of actin cytoskeleton dynamics have long been recognized as valuable molecular probes for dissecting complex mechanisms of cellular function. More recently, their potential use as chemotherapeutic drugs has become a focus of scientific investigation. The primary focus of this review is the molecular mechanism by which different actin-targeting natural products function, with an emphasis on structural considerations of toxins for which high-resolution structural information of their interaction with actin is available. By comparing the molecular interactions made by different toxin families with actin, the structural themes of those that alter filament dynamics in similar ways can be understood. This provides a framework for novel synthetic-compound designs with tailored functional properties that could be applied in both research and clinical settings.

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“…In addition, we demonstrated that the C(1)-C(4) enone-containing subunit of this natural product plays a pivotal role in covalent modification of cellular actin, which further enhances the cytotoxicity of the corresponding bistramide-based compounds. Our study provides comprehensive characterization of the unique mode of action of bistramide A and identifies structural requirements of bistramides that are responsible for severing actin filaments and inhibiting growth of cancer cells in vitro and in vivo (18)(19)(20).…”

mentioning

confidence: 99%

The dual mode of action of bistramide A entails severing of filamentous actin and covalent protein modification

Rizvi¹,

Courson

Keller³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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This study provides comprehensive characterization of the mode of action of bistramide A and identifies structural requirements of bistramide-based compounds that are responsible for severing actin filaments and inhibiting growth of cancer cells in vitro and in vivo. We rationally designed and assembled a series of structural analogs of the natural product, including a fluorescently labeled conjugate. We used TIRF microscopy to directly observe actin filament severing by this series of small molecules, which established that the combination of the spiroketal and the amide subunits was sufficient to enable rapid actin filament disassembly in vitro. In addition, we demonstrated that the enone subunit of bistramide A is responsible for covalent modification of the protein in vitro and in A549 cells, resulting in further increase in the cytotoxicity of the natural product. Our results demonstrate that bistramide A elicits its potent antiproliferative activity by a dual mechanism of action, which entails both severing of actin filaments and covalent sequestration of monomeric actin in the cell.cytoskeleton ͉ natural products ͉ cytotoxicity

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Bistramides A, B, C, D, and K: A New Class of Bioactive Cyclic Polyethers from Lissoclinum bistratum

Cited by 77 publications

References 5 publications

Species specificity of symbiosis and secondary metabolism in ascidians

Species specificity of symbiosis and secondary metabolism in ascidians

Actin-targeting natural products: structures, properties and mechanisms of action

The dual mode of action of bistramide A entails severing of filamentous actin and covalent protein modification

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