Imidazole及びthiazole系化合物のCu(II)キレート誘導体の活性酸素消去作用並びに脂質過酸化抑制作用について

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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 (ClO_4)_2 also have the same activity. Present paper describes the scavenging mechanisms of the Cu (II) chelates and Cu (ClO_4)_2 on active oxygen species. Phenazine methosulfate-NADH system was used as a SO generation system, and the resulting H_2O_2 and ・OH were measured. Cu (ClO_4)_2 and other Cu (II) chelates, which are estimated to produce ・OH from H_2O_2 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 H_2O_2 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 H_2O_2 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.
1993-10-31