Biological activity evaluation and molecular docking study of chromone derivatives as cyclooxygenase-2 inhibitors

Abstract

© 2017, Springer Science+Business Media New York. A series of chromone derivatives have been evaluated as potential cyclooxygenase-2 (COX-2) inhibitors. The four most potent compounds, 48, 41, 39, and 35 displayed IC50values of 3.30, 6.86, 7.36 and 7.46 µM, respectively. Compounds 35 and 38 showed higher selectivity for COX-2 (selectivity index, SI = 7.48 and 5.46, respectively) than celecoxib (SI = 4.17 in the same test) whereas compound 39 showed comparable selectivity (SI = 4.19) to celecoxib. The molecular volumes of compounds 35 (312.84 Å3) and 38 (314.18 Å3) were similar to celecoxib (299.28 Å3) but larger than ibuprofen (211.83 Å3). Docking results were in good agreement with the experimental biological data in terms of evaluation of binding energy and binding mode. Compounds 35, 38, and 39 had higher binding affinity against COX-2 (binding energy between −9.77 and −11.42 kcal/mole) than COX-1 (binding energy between −6.28 and −7.88 kcal/mole). These three chromone compounds also displayed active conformation in the same orientation as that of celecoxib. Thus, compounds in this series has the potential to be a new class of selective COX-2 inhibitor.