Mevalonic acid analogs as inhibitors of cholesterol biosynthesis.
A series of 20 mevalonic acid analogs was synthesized and tested for their ability to inhibit cholesterol biosynthesis from [2-14C]-mevalonate in rat liver homogenates. Removal of the 5-hydroxyl group from mevalonic acid produced an active inhibitor, 3-hydroxy-3-methylpentanoic acid. Removal of the 3-hydroxyl group, addition of an aromatic group in the 3-position, or insertion of a double bond reduced inhibitory activity. Compounds with an aromatic group or halide on the 5-position were active inhibitors. The most active inhibitor was 5-phenylpentanoic acid, with 50% inhibition at 0.064 mM.
D000818:Animals; D000924:Anticholesteremic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002784:Cholesterol / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism; D008297:Male; D008798:Mevalonic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D000924:Anticholesteremic Agents; D002784:Cholesterol; D008798:Mevalonic Acid