Epi-cochlioquinone A, a Novel Acyl-CoA: Cholesterol Acyltransferase Inhibitor Produced by Stachybotrys bisbyi.

Abstract

A novel acyl-CoA : cholesterol acyltransferase (ACAT) inhibitor, designated epi-cochlioquinone A has been isolated from the fermentation broth of Stachybotrys bisbyi SANK17777. The molecular formula, physicochemical properties, NMRspectroscopic analysis and X-ray crystallographic analysis revealed that this compoundwas a stereoisomer of cochlioquinone A, which has been previously reported as a nematocidal agent. It inhibited ACATactivity in an enzyme assay using rat liver microsomes with an IC50 value of 1.7pu. However, it showed about 10-fold less potent inhibitory effect on plasma lecithin cholesterol acyltransferase (LCAT) than on ACAT. In addition, it inhibited in vivo cholesterol absorption in rats by 50% at 75mg/kg.

Stemphones, Novel Potentiators of Imipenem Activity against Methicillin-resistant Staphylococcus aureus, Produced by Aspergillus sp. FKI-2136

“…Compounds of stemphone family have been reported to show various biological activities including: nematocidal activity of cochlioquinone A [16]; inhibitory activity against diacylglycerol acyltransferase by cochlioquinones [17]; and inhibitory activity against cholesterol acyltransferase by epi-cochlioquinone [18]. In this report, we showed that stemphones B and C as well as cochlioquinone D exhibited activity as potentiator of b -lactam imipenem against MRSA.…”

The Mechanism of Action of Bufalin in Inhibition of Lipid Droplet Accumulation in Mouse Macrophages

“…24) On the other hand, other steroids, such as epi-cochlioquinone and (20R)-protopanaxadiol, inhibit ACAT activity. 29,30) In this study, we demonstrated that bufalin, a different type of steroid having a delta lactone ring at the C17 position, also inhibits postlysosomal cholesterol metabolism and leads to reduction of lipid droplets in mouse macrophages.…”

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

“…The results using pregnenolone indicated that the inhibition site of pentacecilides is between the point of cholesterol departure from lysosomes and the point of cholesterol esterification in the endoplasmic reticulum. As epicochlioquinone, whose carbon skeleton and configuration are very similar to those of pentacecilides, is known to inhibit acyl-CoA: cholesterol acyltransferase (ACAT) activity, 16 the effect of pentacecilides on ACAT activity was studied. For this purpose, microsomes prepared from mouse macrophages were used as an enzyme source.…”