TERPENDOLES, NOVEL ACAT INHIBITORS PRODUCED BY ALBOPHOMA-YAMANASHIENSIS .1. PRODUCTION, ISOLATION AND BIOLOGICAL PROPERTIES

A series of new acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor s termed terpendoles were isolated from the culture broth of a fungal strain FO-2546 which was proposed to belong to a new genus designated as Albophoma yamanashiensis. Among four structurally related terpendol es, terpendole C showed the most potent ACAT inhibitory activity with an IC50 value of 2.1 mu M in an in vitro enzyme assay, followed by ter pendoles D (IC50: 3.2 mu M). A (15.1 mu M) and B (26.8 mu M). Evaluati on of their ACAT inhibition in the cell assay using J774 macrophages i ndicated that terpendole D exhibited the highest specificity (cytotoxi city vs. ACAT inhibition) among microbial ACAT inhibitors we discovere d so far.