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

J Antibiot (Tokyo). 2009 Apr;62(4):195-200. doi: 10.1038/ja.2009.18. Epub 2009 Mar 20.

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(50) values of 3.65 and 4.76 microM 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CHO Cells
  • Cholesterol / metabolism
  • Cholesterol Esters / biosynthesis
  • Chromatography, High Pressure Liquid
  • Cricetinae
  • Cricetulus
  • Culture Media
  • Fermentation
  • Hypolipidemic Agents / isolation & purification
  • Hypolipidemic Agents / pharmacology*
  • Lipid Metabolism / drug effects*
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / metabolism*
  • Mice
  • Penicillium / classification
  • Penicillium / metabolism*
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology*
  • Spectrophotometry, Ultraviolet
  • Sterol O-Acyltransferase / metabolism

Substances

  • Cholesterol Esters
  • Culture Media
  • Hypolipidemic Agents
  • Sesquiterpenes
  • pentacecilide A
  • pentacecilide B
  • pentacecilide C
  • Cholesterol
  • Sterol O-Acyltransferase