STRUCTURE-ACTIVITY RELATIONSHIP OF CAFFEIC ACID ANALOGS ON XANTHINE-OXIDASE INHIBITION

Caffeic acid has been reported to have activity on xanthine oxidase in hibition which is related to several diseases, e.g. gout, hepatitis an d tumors. Based on this study, the a, beta-unsaturated COOH moiety in the molecule of caffeic acid plays a very important role on the xanthi ne oxidase inhibition because hydrocaffeic acid was inactive and the a ctivities 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 contributio n to the activity, e.g. trans-cinnamic acid in which the absence of th e phenolic OH group in the structure reduced its activity as compared with caffeic acid. Ferulic acid, isoferulic acid and 3,4-dimethoxy cin namic acid also had reduced activity due to the methoxy groups replaci ng the phenolic OH group in the structures. However, m-coumaric acid d isplayed the strongest activity (IC50 = 63.31 mu M) and induced uncomp etitive inhibition with respect to the substrate xanthine (Ki = 21.568 mu M). Caffeic acid (ICS, = 74.6 mu M) showed the second strongest ac tivity, followed by p-coumaric acid (IC50 = 111.09 mu M).