Effects of 19-Oxygenated Lanosterol Derivatives on 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase Activity and Lanosterol Demethylase Activity

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The effects of 19-oxygenated lanosterol derivatives on lanosterol 14α-demethylase (P-450_<14DM>) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity were studied. 3β-Hydroxylanost-9 (11)-en-19-oic acid (6) was found to be an effective inhibitor (IC_<50> : 0.5 μM) of P-450_<14DM> in the reconstituted system using purified pig liver P-450_<14DM> and was most active in inhibiting HMG-CoA reductase activity (IC_<50> : 1.0μM) in mouse L cells. In [2-^<14>C] acetate incorporation studies using mouse L cells, 6 was found to reduce the incorporation of acetate into C_<27>-sterol (desmosterol) with a concomitant increase in radiolabeled C_<30>-sterols. These results demonstrate that 6 is a dual-action inhibitor of cholesterol biosynthesis.
公益社団法人日本薬学会の論文
1996-01-15