Abstract
A systematic screen for new natural products that displayed antifungal activity by inhibition of fungal fatty acid synthase (FAS) led to the discovery of two new fungal metabolites, designated CT2108A (1) and CT2108B (2). The metabolites were produced by Penicillium solitum (Westling) strain CT2108 and were classified as azaphilones. The structures of these new metabolites were determined using a variety of 1D and 2D NMR experiments, including COSY, HMQC, and HMBC. The chemical conversion of CT2108A to CT2108B was effected using WCl(6). The related metabolite, patulodin (3), was also isolated from the fermentation culture of this P. solitum isolate. Both new compounds inhibited fungal FAS, and neither was found to significantly inhibit human FAS activity.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antifungal Agents / chemistry
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Antifungal Agents / isolation & purification*
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Antifungal Agents / pharmacology
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Benzopyrans / chemistry
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Benzopyrans / isolation & purification*
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Benzopyrans / pharmacology
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Candida albicans / drug effects
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / isolation & purification*
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Enzyme Inhibitors / pharmacology
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Epoxy Compounds / chemistry
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Epoxy Compounds / isolation & purification*
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Epoxy Compounds / pharmacology
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Fatty Acid Synthases / antagonists & inhibitors*
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Fermentation
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Humans
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Inhibitory Concentration 50
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Molecular Structure
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Nuclear Magnetic Resonance, Biomolecular
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Penicillium / chemistry*
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Penicillium / metabolism
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Pyrans*
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / enzymology
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Wyoming
Substances
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Antifungal Agents
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Benzopyrans
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CT2108A
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CT2108B
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Enzyme Inhibitors
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Epoxy Compounds
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Pyrans
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patulodin
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Fatty Acid Synthases