摘要：The effects of 19-oxygenated lanosterol derivatives on lanosterol 14α-demethylase (P-45014DM) 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 (IC50 : 0.5 μM) of P-45014DM in the reconstituted system using purified pig liver P-45014DM and was most active in inhibiting HMG-CoA reductase activity (IC50 : 1.0μM) in mouse L cells. In [2-14C] acetate incorporation studies using mouse L cells, 6 was found to reduce the incorporation of acetate into C27-sterol (desmosterol) with a concomitant increase in radiolabeled C30-sterols. These results demonstrate that 6 is a dual-action inhibitor of cholesterol biosynthesis.
