STRUCTURE-ACTIVITY RELATIONSHIP AND CLASSIFICATION OF FLAVONOIDS AS INHIBITORS OF XANTHINE-OXIDASE AND SUPEROXIDE SCAVENGERS

The structure-activity relationship of flavonoids as inhibitors of xan thine oxidase and as scavengers of the superoxide radical, produced by the action of the enzyme xanthine oxidase, was investigated. The hydr oxyl groups at C-5 and C-7 and the double bond between C-2 and C-3 wer e essential for a high inhibitory activity on xanthine oxidase. Flavon es showed slightly higher inhibitory activity than flavonols. All flav onoid derivatives except isorhamnetin (30) were less active than the o riginal compounds. For a high superoxide scavenging activity on the ot her hand, a hydroxyl group at C-3' in ring B and at C-3 were essential . According to their effect on xanthine oxidase and as superoxide scav engers, the flavonoids could be classified into six groups: superoxide scavengers without inhibitory activity on xanthine oxidase (category A), xanthine oxidase inhibitors without any additional superoxide scav enging activity (category B), xanthine oxidase inhibitors with an addi tional superoxide scavenging activity (category C), xanthine oxidase i nhibitors with an additional pro-oxidant effect on the production of s uperoxide (category D), flavonoids with a marginal effect on xanthine oxidase but with a prooxidant effect on the production of superoxide ( category E), and finally, flavonoids with no effect on xanthine oxidas e or superoxide (category F).