Inhibition of sterol biosynthesis in L cells and mouse liver cells by 15-oxygenated sterols.
Described herein are the chemical syntheses of 5alpha-cholest-8(14-en-3beta-ol-15-one, 14alpha-methyl-5alpha-cholest-7-en-3beta-ol-15-one, 3beta-methoxy-14alpha-methyl-5alpha-cholest-7-en-15-one, 3beta-methoxy-14alpha-methyl-5alpha-cholest-7-en-15beta-ol, 3beta-methoxy-14alpha-methyl-15alpha-ol, and 5alpha-cholest-8(14)-en-3beta, 7xi,15xi-triol. The effects of these compounds and of 5alpha-cholest-8(14)-en-3beta,15beta-diol, 5alpha-cholest-8(14)-en-3beta,15alpha-diol, 5alpha,14beta-cholest-7-en-3beta,15beta-diol, 5alpha,14beta-cholest-7-en-3beta, 15alpha-diol, 14alpha-methyl-5alpha-cholest-7-en-3beta,15beta-diol, and 14alpha-methyl-5alpha-cholest-7-en-3beta,15alpha-diol on sterol synthesis in L cells and primary cultures of fetal mouse liver cells grown in serum-free media have been studied. With the exception of 3beta-methoxy-5alpha-cholest-7-en-15-one, all of the compounds were found to be potent inhibitors of sterol synthesis. With a few exceptions, the concentrations required to cause a 50% reduction in sterol synthesis were similar to those required to cause a 50% reduction in the level of HMG-CoA reductase activity.
D002478:Cells, Cultured; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007739:L Cells / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D013261:Sterols / Q000096:biosynthesis*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013261:Sterols; D002784:Cholesterol