Pentacecilides, new inhibitors of lipid droplet formation in mouse macrophages, produced by Penicillium cecidicola FKI-3765-1: I. Taxonomy, fermentation, isolation and biological properties.
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.
Yamazaki
Hiroyuki
H
Graduate School of Pharmaceutical Sciences, Kitasato University, Shirokane, Tokyo, Japan.
Kobayashi
Kakeru
K
Matsuda
Daisuke
D
Nonaka
Kenichi
K
Masuma
Rokuro
R
Omura
Satoshi
S
Tomoda
Hiroshi
H
D000818:Animals; D016466:CHO Cells; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000096:biosynthesis; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003412:Cricetulus; D003470:Culture Media; D005285:Fermentation; D000960:Hypolipidemic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010407:Penicillium / Q000145:classification / Q000378:metabolism*; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D002785:Sterol O-Acyltransferase / Q000378:metabolism
D002788:Cholesterol Esters; D003470:Culture Media; D000960:Hypolipidemic Agents; D012717:Sesquiterpenes; C544291:pentacecilide A; C544292:pentacecilide B; C544290:pentacecilide C; D002784:Cholesterol; D002785:Sterol O-Acyltransferase