Design, synthesis and biological activity of new cyclooxygenase inhibitors

In this present work, new chalcone and pyrazoline derivatives (3a-3i, 4a-4i) were synthesized and examined for their inhibition potential against cyclooxygenase enzymes. Their structures were elucidated by IR, 1H NMR, 13C NMR, 2D-NMR and HRMS spectroscopic methods. Enzyme inhibition studies revealed that the chalone derivatives 3a, 3b, 3d, 3e, 3f, 3g, 3h and 3i (IC50= 0,3365-0,1838 µM) showed potent inhibitory activity against COX-2 enzyme as compared with reference compounds celecoxib (IC50= 0,1205 µM), ibuprofen (IC50= 5,3274 μM) and nimesulide (IC50= 1,6838 μM). Among these compounds, 1-[4-(methylsulfonyl)phenyl]-3-(2,3-dichlorophenyl)prop-2-en-1-one (3e), 1-[4-(methyl sulfonyl)phenyl]-3-(2,4-dichlorophenyl)prop-2-en-1-one (3f) and 1-[4-(methylsulfonyl) phenyl]-3-(2-chloro-6-fluorophenyl)prop-2-en-1-one (3h) became prominent with the IC50 values of 0,2133 µM, 0,1933 µM and 0,1838 µM, respectively. According to molecular docking studies of the most effective compounds, it was found that the compounds interact with amino acids that are important in COX-2 selectivity such as Arg499 and Phe504.