Pentacecilides, new inhibitors of lipid droplet formation in mouse macrophages, produced by Penicillium cecidicola FKI-3765-1: I. Taxonomy, fermentation, isolation and biological properties

Abstract

New compounds designated pentacecilides A to C were isolated from the fermentation broth of Penicillium cecidicola FKI-3765-1 by solvent extraction, silica gel column chromatography and preparative HPLC. Pentacecilides A and B dose-dependently inhibited lipid droplet formation in mouse macrophages. Furthermore, pentacecilides A and B were found to inhibit the synthesis of cholesteryl ester in mouse macrophages with respective IC"5"0 values of 3.65 and 4.76 μM without any cytotoxic effect, but pentacecilide C showed almost no activity. The study of the mechanism of action strongly suggested that pentacecilides A and B inhibit acyl-CoA: cholesterol acyltransferase activity in macrophages. © 2009 Japan Antibiotics Research Association All rights reserved.