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CT2108A and B: New fatty acid synthase inhibitors as antifungal agents
Jodi A Laakso1, Robert Raulli, Gail E McElhaney-Feser
1Panlabs, Incorporated, 11804 North Creek Parkway South, Bothell, Washington 90811-8805, USA.
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.
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