Inhibition of sterol biosynthesis in animal cells by 14 alpha-alkyl-substituted 15-oxygenated sterols.
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.
D000818:Animals; D002478:Cells, Cultured; D002782:Cholestenes / Q000494:pharmacology*; D002783:Cholestenones / Q000494:pharmacology*; D005333:Fetus; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007739:L Cells / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D013261:Sterols / Q000096:biosynthesis*; D013329:Structure-Activity Relationship
D002782:Cholestenes; D002783:Cholestenones; D013261:Sterols; D006903:Hydroxymethylglutaryl CoA Reductases