Hypocholesterolemic and antiaggregatory properties of 2-hydroxytetronic acid redox analogues an their relationship to clofibric acid.
A rationale is presented for investigating aci-reductone 2-hydroxytetronic acids as antilipidemic drugs. These compounds are lipophilic Brönsted acids capable of forming water-soluble anions having biologically relevant redox potentials. The inhibitory effects of 4-(4-chlorophenyl)-2-hydroxytetronic acid (2a) on human platelet aggregation and [14C]serotonin secretion were compared with clofibric acid (1b), the hydrolysis product of clofibrate (1a). In cholesterol-fed rats, this analogue was superior to clofibrate as a hypocholesterolemic drug and modifier of heparin-MnCl2 precipitated lipoprotein cholesterol to alpha-lipoprotein cholesterol ratios. Whereas clofibrate (1a) produced hepatomegaly, this effect was not observed for the tetronic acid 2a.
D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D002994:Clofibrate / Q000494:pharmacology*; D005663:Furans / Q000494:pharmacology*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D000924:Anticholesteremic Agents; D005663:Furans; D008074:Lipoproteins; D002784:Cholesterol; D002994:Clofibrate