Structure−Activity Relationship and Classification of Flavonoids as Inhibitors of Xanthine Oxidase and Superoxide Scavengers

Abstract

The structure-activity relationship of flavonoids as inhibitors of xanthine oxidase and as scavengers of the superoxide radical, produced by the action of the enzyme xanthine oxidase, was investigated. The hydroxyl groups at C-5 and C-7 and the double bond between C-2 and C-3 were essential for a high inhibitory activity on xanthine oxidase. Flavones showed slightly higher inhibitory activity than flavonols. All flavonoid derivatives except isorhamnetin (30) were less active than the original compounds. For a high superoxide scavenging activity on the other 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 scavengers, 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 scavenging activity (category B), xanthine oxidase inhibitors with an additional superoxide scavenging activity (category C), xanthine oxidase inhibitors with an additional pro-oxidant effect on the production of superoxide (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 oxidase or superoxide (category F).

On the vasoprotective mechanisms underlying novel β-phosphorylated nitrones: Focus on free radical characterization, scavenging and NO-donation in a biological model of oxidative stress

“…First, the xanthine oxidase inhibiting activity of PPNs and four parent phenolic acids was assessed using a reported procedure [49]. Each compound (ranging 1−100 µM) was incubated at 37 °C for 30 min with a mixture of xanthine (50 µM)-xanthine oxidase (1.25 mU/mL) in DMSO (1%)-supplemented PBS (200 mM, pH 7.5) and uric acid formation was monitored spectrophotometrically.…”

Free Radical Scavenging Properties of Skin and Pulp Extracts of Different Grape Cultivars In Vitro and Attenuation of H2O2-Induced Oxidative Stress in Liver Tissue Ex Vivo

“…Proteins [13], sugar [14], ascorbic acid [15], polyphenols [16] and flavonoids [17] contents were determined.…”

Antioxidant activity in vitro of two aromatic compounds from Caesalpinia sappan L

“…The hydroxyl radical scavenging activity was determined using deoxyribose assay as described [13]. 2-deoxyribose was oxidized and degraded into thiobarbituric acid reactive substances by • OH generated from the Fenton reaction.…”

“…After the incubation, 1 mL of TCA (2.8%, w/v) and thiobarbituric acid (1%, w/v) were added and the mixture was boiled for 10 min. After cooling on ice, absorbance at 532 nm of the reaction mixture was measured [13].…”