Inhibitors of sterol biosynthesis. Synthesis and activities of ring C oxygenated sterols.
The chemical syntheses of a number of C27 ring C oxygenated sterols have been pursued to permit evaluation of their activity in the inhibition of sterol biosynthesis in cultured mammalian cells. Thus, 5 alpha-cholest-7-ene-3 beta, 11 alpha-diol, 3 alpha-hydroxy-5 alpha-cholest-9(11)-en-12-one, and the previously unreported 11 alpha-hydroxy-5 alpha-cholest-7-en-3-one, 5 alpha-cholest-9(11)-ene-3,12-dione, and 3 beta-hydroxy-5 alpha-cholest-9 (11)-en-12-one have been synthesized. The effects of these compounds on the synthesis of digitonin-precipitable sterols from labeled acetate in mouse L cells and on the levels of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity in the same cells have been investigated and compared with previously published data on other ring C oxygenated sterols. 5 alpha-Cholest-7-ene-3 beta, 11 alpha-diol was shown to be the most potent inhibitor of sterol synthesis.
Schroepfer
G J
GJ
Department of Biochemistry, Rice University, Houston, TX 77251.
Parish
E J
EJ
Kandutsch
A A
AA
D000085:Acetates / Q000378:metabolism; D000818:Animals; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007202:Indicators and Reagents; D007739:L Cells / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D013055:Spectrophotometry, Infrared; D013261:Sterols / Q000096:biosynthesis / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000085:Acetates; D007202:Indicators and Reagents; D013261:Sterols; D006903:Hydroxymethylglutaryl CoA Reductases