RESUMO
From a study on the biological activity of fungal stemphones and their derivatives, five derivatives having an O-alkyl moiety at C-11 of stemphone C were found to inhibit lipid droplet accumulation in macrophages without any cytotoxic effect. Among the derivatives, those having O-isopropyl and O-isobutyl were the most potent inhibitors by blocking the synthesis of both cholesteryl ester (CE) and triacylglycerol (TG), the main constituents of lipid droplets in macrophages.
Assuntos
Benzoquinonas/farmacologia , Células Espumosas/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Animais , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Colesterol/metabolismo , Ésteres do Colesterol/biossíntese , Diacilglicerol O-Aciltransferase/antagonistas & inibidores , Diacilglicerol O-Aciltransferase/metabolismo , Células Espumosas/efeitos dos fármacos , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Camundongos , Esterol O-Aciltransferase/antagonistas & inibidores , Esterol O-Aciltransferase/metabolismo , Triglicerídeos/biossínteseRESUMO
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.