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 μM, 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 μM) and a novel chalcone (13) (IC₅₀, 2.4 μM) displayed strong xanthine oxidase inhibitory activity that is comparable to allopurinol (IC₅₀, 2.5 μM). 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.Graphical abstractThe chalcone derivatives as potential non-purine xanthine oxidase inhibitors.