Inhibition of sterol biosynthesis in animal cells by 14 alpha-alkyl-substituted 15-oxygenated sterols.
Cells-Cultured, Cholestenes, Cholestenones, Fetus, Hydroxymethylglutaryl-CoA-Reductases: me, L-Cells: de, me, Liver: de, me, Mice, Sterols: bi, Structure-Activity-Relationship, SUPPORT-U-S-GOVT-P-H-S
J-Lipid-Res. 1979 Nov; 20(8):994-8.
Reported herein are the results of investigations of the effects of a number of 14 alpha-alkyl-substituted 15-oxygenated sterols, prepared by chemical synthesis, on sterol biosynthesis and the levels of 3-hydroxy-3-methylglutaryl CoA reductase activity in L cells and in primary cultures of fetal mouse liver cells grown in serum-free media. Several of the compounds, most notably 14 alpha-ethyl-5 alpha-cholest-7-en-3 beta, 15 alpha-diol and 14 alpha-ethyl-5 alpha-cholest-7-en-15 alpha-ol-3-one, were found to be extraordinarily potent inhibitors of sterol synthesis in these cells. For example, the latter compound caused a 50% inhibition of the incorporation of labeled acetate into digitonin-precipitable sterols in L cells in culture at a concentration of 6 X 10(-9) M.
Schroepfer, G J.; Parish, E J.; Tsuda, M; Raulston, D L.; and Kandutsch, A A., " Inhibition of sterol biosynthesis in animal cells by 14 alpha-alkyl-substituted 15-oxygenated sterols." (1979). Faculty Research 1970 - 1979. 983.
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