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.