Epi-cochlioquinone A, a novel acyl-CoA : cholesterol acyltransferase inhibitor produced by Stachybotrys bisbyi.
نویسندگان
چکیده
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.
منابع مشابه
Gypsetin, a new inhibitor of acyl-CoA:cholesterol acyltransferase produced by Nannizzia gypsea var. incurvata IFO 9228. I. Fermentation, isolation, physico-chemical properties and biological activity.
A novel inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), designated gypsetin, was isolated from the cultured broth of Nannizzia gypsea var. incurvata IFO 9228 by solvent extraction, silica gel chromatography and crystallization. Gypsetin inhibited rat liver microsomal ACAT activity competitively with respect to the substrate oleoyl-CoA with an apparent Ki value of 5.5 microM. In cultur...
متن کاملGLISOPRENINS, NEW INHIBITORS OF ACYL-CoA: CHOLESTEROL ACYLTRANSFERASE PRODUCED BY Gliocladium sp. FO-1513 I. PRODUCTION, ISOLATION AND PHYSICO-CHEMICAL AND BIOLOGICAL PROPERTIES HlROSHI TOMODA, XlN-Hui HUANG, HlROYUKI NlSHIDAf, ROKURO MASUMA,
Gliocladium sp. FO-1513 was found to produce novel inhibitors of acyl-CoA: cholesterol acyltransferase (ACAT). Twoactive compounds, designated glisoprenins A and B, were isolated from the culture broth of the producing strain by a conventional method. The IC50 values of glisoprenins A and B for ACATactivity were 46 and 61fiM in an enzyme assay using rat liver microsomes, and 1.2 and 0.57 /^M in...
متن کاملLateritin, a new inhibitor of acyl-CoA:cholesterol acyltransferase produced by Gibberella lateritium IFO 7188.
A new inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), designated lateritin, was isolated from the mycelial cake of Gibberella lateritium IFO 7188 by successive purification procedure of solvent extraction, silica gel column chromatography and reverse phase HPLC. Spectroscopic analyses of the compound yielded 4-methyl-6-(1-methylethyl)-3-phenylmethyl-1,4-perhydrooxazine-2,5- dione as t...
متن کاملEffect of lovastatin on acyl-CoA: cholesterol O-acyltransferase (ACAT) activity and the basolateral-membrane secretion of newly synthesized lipids by CaCo-2 cells.
Lovastatin, a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity, was used to study the regulation of cholesterol metabolism and the basolateral-membrane secretion of triacylglycerol and cholesterol in the human intestinal cell line CaCo-2. At 0.1 microgram/ml, lovastatin decreased 3H2O incorporation into cholesterol by 71%. In membranes prepared from ce...
متن کاملPenicillium griseofulvum F1959, high-production strain of pyripyropene a, specific inhibitor of acyl-CoA: cholesterol acyltransferase 2.
Acyl-coenzyme A: cholesterol acyltransferase (ACAT) catalyzes cholesterol esterification and plays an important role in the intestinal absorption of cholesterol, hepatic production of lipoproteins, and accumulation of cholesteryl ester within cells. During the course of screening to find ACAT inhibitors from microbial sources, the present authors isolated pyripyropene A from Penicillium griseof...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The Journal of antibiotics
دوره 49 5 شماره
صفحات -
تاریخ انتشار 1996