Structure-activity relationship of caffeic acid analogues on xanthine oxidase inhibition

Caffeic acid has been reported to have activity on xanthine oxidase inhibition which is related to several diseases, e.g. gout, hepatitis and tumors. Based on this study, the alpha, beta-unsaturated COOH moiety in the molecule of caffeic acid plays a very important role on the xanthine oxidase inhibition because hydrocaffeic acid was inactive and the activities of coniferyl aldehyde and coniferyl alcohol were reduced as compared with ferulic acid. Moreover, chlorogenic acid showed a weaker activity than caffeic acid. On the other hand, the phenolic OH group present in the molecule of caffeic acid makes an important contribution to the activity, e.g. transcinnamic acid in which the absence of the phenolic OH group in the structure reduced its activity as compared with caffeic acid. Ferulic acid, isoferulic acid and 3,4-dimethoxy cinnamic acid also had reduced activity due to the methoxy groups replacing the phenolic OH group in the structures. However, m-coumaric acid displayed the strongest activity (IC50 = 63.31 microM) and induced uncompetitive inhibition with respect to the substrate xanthine (Ki = 21.568 microM). Caffeic acid (IC50 = 74.6 microM) showed the second strongest activity, followed by p-coumaric acid (IC50 = 111.09 microM).