Active Oxygen Scavenging Activity of Cu (II) Chelates of Imidazole and Thiazole Derivatives and Their Antioxidant Effect on Lipid Peroxidation In Vitro.

Abstract

In the previous paper, we reported that Cu (II) chelates of imidazole and thiazole derivatives have superoxide (SO) and OH radical (·OH) scavenging activities, and that Cu (ClO4)2 also have the same activity. Present paper describes the scavenging mechanisms of the Cu (II) chelates and Cu (ClO4)2 on active oxygen species. Phenazine methosulfate-NADH system was used as a SO generation system, and the resulting H2O2 and ·OH were measured. Cu (ClO4)2 and other Cu (II) chelates, which are estimated to produce ·OH from H2O2 by the Fenton reaction, generated so much amount of ·OH. But, in the case of Cu (II) chelates of N-methyl-N'-[2-(imidazol-4-yl) methylthioethyl] thiourea (I-2) and 3-(2-thioureidothiazol-4-ylmethylthio) propionitrile (T-3), the amounts of H2O2 and ·OH produced were less than those produced in the absent of the chelates. Therefore, it seems that these chelates have not only superoxide scavenging activity but also H2O2 scavenging activity, which is not followed by OH radical formation. Further, Cu (II) chelates of I-2 and T-3 showed antioxidant effects on the rat liver microsomal peroxidation induced by Fe (III)-ADP-NADPH. Finally, T-3 did not inhibit the enzymatic activity of NADPH-dependent cytochrome P-450 reductase.