Design, synthesis, biological evaluation, and docking studies of some novel chalcones as selective COX‐2 inhibitors
Betül Kaya Çavuşoğlu, Begüm Nurpelin Sağlık, Ulviye Acar Çevik, Derya Osmani̇ye, Serkan Levent, Yusuf Özkay, Zafer Asım Kaplancıklı
Abstract
Abstract A new series of chalcones ( 1−9 ) possessing an SO 2 CH 3 COX‐2 pharmacophore at the para position of the C‐1 phenyl ring was synthesized via the Claisen–Schmidt condensation reaction and examined for their inhibition potential against cyclooxygenase (COX) enzymes. Their structures were elucidated by infrared, 1 H NMR (nuclear magnetic resonance), 13 C NMR, and high‐resolution mass spectroscopic methods. Enzyme inhibition studies revealed that most of the compounds showed a moderate‐to‐strong inhibitory activity (IC 50 = 0.18−0.34 μM) against the COX‐2 enzyme as compared with celecoxib (IC 50 = 0.12 μM), ibuprofen (IC 50 = 5.33 μM), and nimesulide (IC 50 = 1.68 μM). Among these compounds, 1‐[4‐(methylsulfonyl)phenyl]‐3‐(2,3‐dichlorophenyl)prop‐2‐en‐1‐one ( 5 ), 1‐[4‐(methylsulfonyl)phenyl]‐3‐(2,4‐dichlorophenyl)prop‐2‐en‐1‐one ( 6 ), and 1‐[4‐(methylsulfonyl)phenyl]‐3‐(2‐chloro‐6‐fluorophenyl)prop‐2‐en‐1‐one ( 8 ) became prominent with IC 50 values of 0.21, 0.19, and 0.18 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.