Abstract

Twelve new heptaketides, biatriosporins A-L (1-12), biatriosporin M (13) (a ramulosin derivative), and 19 known compounds (14-32) were isolated from the endolichenic fungus Biatriospora sp. (8331C). The structures of these compounds were determined by analyzing MS and NMR data. The absolute configurations of compounds 1, 2, 7, and 9 were determined by single-crystal X-ray diffraction analysis, whereas compound 10 was deduced with Mosher's method. Four of the compounds were active in an antifungal assay. The most potent compound, compound 4, also sensitized clinically derived azole-resistant Candida albicans strains to fluconazole (FLC). A mechanistic investigation revealed that 4 inhibited the function of efflux pumps and reduced the transcriptional expression of the efflux-pump-related genes CDR1 and CDR2.

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