Abstract
Novel synthetic oxysterols (22S,23S)-3β-hydroxy-22,23-oxido-5α-ergost-8(14)-en-15-one (I) and (22R,23R)-3β-hydroxy-22,23-oxido-5α-ergost-8(14)-en-15-one (II) efficiently inhibited cholesterol biosynthesis in human hepatoma Hep G2 cells during short-term incubation in a serum free medium (IC50 values of 1.9 ± 0.2 and 0.6 ± 0.2 μ M, respectively). Cultivation of Hep G2 cells in the presence of 5 μM concentration of either (I) or (II) resulted in significant reduction of cholesterol biosynthesis (52% and 57% from control), and also changes in biosynthesis of fatty acids, triglycerides, and cholesteryl esters. Compounds (I) and (II) stimulated transformation of exogenous cholesterol to polar products secreted into the culture medium (156 % and 175% of control) as it that was shown in experiments in Hep G2 cells prelabeled with [3H]cholesterol.
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