Design and synthesis of chalcone derivatives as potential non-purine xanthine oxidase inhibitors

Background: Based on some previous research, the chalcone derivatives exhibited potent xanthine oxidase inhibitory activity, e.g. sappanchalcone (7), with IC50 value of 3.9 mu M, was isolated from Caesalpinia sappan. Therefore, objectives of this research are design and synthesis of 7 and other chalcone derivatives by Claisen-Schmidt condensation and then evaluate their XO inhibitory activity. Results: Fifteen chalcone derivatives were synthesized by Claisen-Schmidt condensation, and were evaluated for XO inhibitory activity. Nine out of 15 synthetic chalcones showed inhibitory activity (3; 5-8; 10-13). Sappanchalcone derivatives (11) (IC50, 2.5 mu M) and a novel chalcone (13) (IC50, 2.4 mu M) displayed strong xanthine oxidase inhibitory activity that is comparable to allopurinol (IC50, 2.5 mu M). The structure-activity relationship of these chalcone derivatives was also presented. Conclusions: It is the first research on synthesis sappanchalcone (7) by Claisen-Schmidt condensation. The overall yield of this procedure was 6.6 %, higher than that of reported procedure (4 %). Design, synthesis, and evaluation of chalcone derivatives were carried out. This result suggests that the chalcone derivative can be used as potential non-purine XO inhibitors.