An in vitro study of the hydroxyl radical scavenging-property of fluvastatin, an HMG-CoA reductase inhibitor

We investigated the in vitro hydroxyl radical scavenging activity of fluvas tatin, a 3-hydroxy-3-methylglutaryl (HMG)- CoA reductase inhibitor. Fluvast atin showed hydroxyl radical scavenging activity as potent as that of dimet hylthiourea and alpha-tocophcrol, which are well-known respectively, as a h ydroxyl radical scavenger and a natural antioxidant, Since this effect was not observed in other HMG-CoA reductase inhibitors, such as pravastatin and simvastatin, the scavenging effect of fluvastatin on hydroxyl radicals wou ld not be a common property of HMG-CoA reductase inhibitors, but is derived from the unique chemical structure of fluvastatin, The hydroxyl radical sc avenging activities of human metabolites of fluvastatin were also determine d. All the tested metabolites possessing the fluorophenyl indole moiety sho wed activity. Among them, the metabolites which possess a phenolic hydroxyl group on the indole moiety showed stronger effects than that of fluvastati n, We suggest that the fluorophenyl indole moiety of fluvastatin is importa nt for manifestation of the activity and that the phenolic hydroxyl group e nhances the potency.