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Design, synthesis, biological evaluation, and docking studies of some novel chalcones as selective COX‐2 inhibitors
Author(s) -
Kaya Çavuşoğlu Betül,
Sağlık Begüm N.,
Acar Çevik Ulviye,
Osmaniye Derya,
Levent Serkan,
Özkay Yusuf,
Kaplancıklı Zafer A.
Publication year - 2021
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.202000273
Subject(s) - chemistry , stereochemistry , pharmacophore , nimesulide , docking (animal) , enzyme , ibuprofen , organic chemistry , biochemistry , pharmacology , medicine , nursing
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.