Oxidation of Flavonoids which Promote DNA Degradation Induced by Bleomycin–Fe Complex

Abstract

Sixteen flavonoids including quercetin and kaempferol and their relatives were examined for their ability to promote DNA degradation induced by the bleomycin (BLM)–Fe complex. Three hydroxyl groups in the flavonoidal nucleus were proposed as a crucial structural requirement for effectively promoting DNA degradation: 1) the C7-hydroxyl substitution in the A-ring; 2) the C4′-hydroxyl substitution in the B-ring; and 3) the C3-hydroxyl substitution in the C-ring. Flavonoids, which lack even one of these hydroxyl substitutions, showed remarkably diminished activity. There was a good correlation (r=0.920, p<0.001) between activity to promote DNA degradation and oxidizability, which was measured following the Fe(III)-induced oxidation of flavonoids themselves, among the 16 flavonoids. The oxidizability of flavonoids which have the crucial hydroxyl substitutions, was remarkably enhanced in the presence compared with the absence of BLM. On the other hand, the extent of oxidation of flavonoids lacking these substitutions was enhanced little or not at all by BLM. No correlation between the Fe(III)-reducing activity and DNA degradation-promoting activity was found among flavonoids satisfying the crucial structural requirements. Furthermore, the correlation between the extent of oxidation of flavonoids and the Fe(III)-reducing activity was not confirmed among these flavonoids. Therefore, it was suggested that Fe(III)-reducing activity was not the only factor determining DNA degradation-promoting activity in flavonoids having the three hydroxyl groups necessary for effectively promoting DNA degradation induced by BLM–Fe complex.