Epi-cochlioquinone A, a novel acyl-CoA : cholesterol acyltransferase inhibitor produced by Stachybotrys bisbyi.
A novel acyl-CoA : cholesterol acyltransferase (ACAT) inhibitor, designated epi-cochlioquinone A has been isolated from the fermentation broth of Stachybotrys bisbyi SANK 17777. The molecular formula, physicochemical properties, NMR spectroscopic analysis and X-ray crystallographic analysis revealed that this compound was a stereoisomer of cochlioquinone A, which has been previously reported as a nematocidal agent. It inhibited ACAT activity in an enzyme assay using rat liver microsomes with an IC50 value of 1.7 microM. 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 75 mg/kg.
Fujioka
T
T
Pharmacology Research Laboratory, Sankyo Co., Ltd., Tokyo, Japan.
Yao
K
K
Hamano
K
K
Hosoya
T
T
Kagasaki
T
T
Furukawa
Y
Y
Haruyama
H
H
Sato
S
S
Koga
T
T
Tsujita
Y
Y
D000818:Animals; D000969:Antinematodal Agents; D016227:Benzoquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005285:Fermentation; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013191:Stachybotrys; D013237:Stereoisomerism; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
D000969:Antinematodal Agents; D016227:Benzoquinones; C066134:cochlioquinone A; D002785:Sterol O-Acyltransferase