PYRIPYROPENES, NOVEL INHIBITORS OF ACYL-CoA: CHOLESTEROL ACYLTRANSFERASE PRODUCED BY Aspergillus fumigatus

I. PRODUCTION, ISOLATION, AND BIOLOGICAL PROPERTIES

Abstract

Aspergillus fumigatus FO-1289, a soil isolate, was found to produce a series of novel inhibitors of acyl-CoA: cholesterol acyltansferase (ACAT). Four active compounds, named pyripyropenes A, B, C and D, were isolated from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography, ODS column chromatography and preparative HPLC. Pyripyropenes A, B, C and D show very potent ACAT inhibitory activity in an enzyme assay system using rat liver microsomes with IC₅₀ values of 58, 117, 53 and 268 nM, respectively.