Terpendoles, Novel AC AT Inhibitors Produced by Albophoma yamanashiemis

I. Production, Isolation and Biological Properties

Abstract

A series of new acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors 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 terpendoles, terpendole C showed the most potent ACAT inhibitory activity with an IC₅₀ value of 2.1 μM in an in vitro enzyme assay, followed by terpendoles D (IC₅₀: 3.2μM), A (15.1.μM) and B (26.8μM). Evaluation of their ACAT inhibition in the cell assay using J774 macrophages indicated that terpendole D exhibited the highest specificity (cytotoxicity vs. ACAT inhibition) among microbial ACAT inhibitors we discovered so far.