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
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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CHO Cells
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Cholesterol / metabolism
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Cholesterol Esters / biosynthesis
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Chromatography, High Pressure Liquid
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Cricetinae
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Cricetulus
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Culture Media
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Fermentation
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Hypolipidemic Agents / isolation & purification
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Hypolipidemic Agents / pharmacology*
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Lipid Metabolism / drug effects*
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Lysosomes / drug effects
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Lysosomes / metabolism
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Macrophages, Peritoneal / drug effects
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Macrophages, Peritoneal / metabolism*
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Mice
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Penicillium / classification
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Penicillium / metabolism*
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Sesquiterpenes / isolation & purification
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Sesquiterpenes / pharmacology*
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Spectrophotometry, Ultraviolet
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Sterol O-Acyltransferase / metabolism
Substances
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Cholesterol Esters
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Culture Media
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Hypolipidemic Agents
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Sesquiterpenes
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pentacecilide A
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pentacecilide B
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pentacecilide C
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Cholesterol
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Sterol O-Acyltransferase