Abstract
In the course of a screening for inositol phosphorylceramide (IPC) synthase inhibitors, the novel inhibitors pleofungins A, B, C, and D were found in a mycelial extract of a fungus, Phoma sp. SANK13899. Purification was performed by 50% methanol and ethyl acetate extraction, reversed phase open-column chromatography, and HPLC separations. Pleofungin A inhibited the IPC synthase of Saccharomyces cerevisiae and Aspergillus fumigatus at IC(50) values of 16 and 1.0 ng/ml, respectively. The inhibitor also suppressed the growth of Candida albicans, Cryptococcus neoformans, and A. fumigatus at MIC values of 2.0, 0.3, and 0.5 mug/ml, respectively. These biological properties indicate that pleofungins belong to a novel class of IPC synthase inhibitors efficacious against A. fumigatus.
MeSH terms
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Antifungal Agents / chemical synthesis
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Antifungal Agents / pharmacology
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Ascomycota / drug effects*
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Ascomycota / enzymology
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Ascomycota / metabolism*
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Aspergillus fumigatus / drug effects
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Aspergillus fumigatus / enzymology
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Candida albicans / drug effects
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Candida albicans / growth & development
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Chromatography, High Pressure Liquid
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Cryptococcus neoformans / drug effects
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Cryptococcus neoformans / growth & development
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Depsipeptides / isolation & purification
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Depsipeptides / pharmacology*
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Enzyme Inhibitors / isolation & purification
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Enzyme Inhibitors / pharmacology*
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Fermentation
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Hexosyltransferases / antagonists & inhibitors*
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Microbial Sensitivity Tests
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / enzymology
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Sphingolipids / biosynthesis
Substances
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Antifungal Agents
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Depsipeptides
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Enzyme Inhibitors
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Sphingolipids
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Hexosyltransferases
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phosphatidylinositol-ceramide phosphoinositol transferase