Pleofungins,Novel Inositol Phosphorylceramide Synthase Inhibitors,from Phoma sp.SANK 13899:I.Taxonomy,Fermentation,Isolation,and Biological Activities

摘要

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 IC50 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 mu g/ml,respectively.These biological properties indicate that pleofungins belong to a novel class of IPC synthase inhibitors efficacious against A.fumigatus.