Design, synthesis, biological evaluation, and docking studies of some novel chalcones as selective COX-2 inhibitors

Kaya Cavusoglu B., SAĞLIK B. N., ACAR ÇEVİK U., OSMANİYE D., LEVENT S., ÖZKAY Y., ...More

ARCHIV DER PHARMAZIE, vol.354, no.3, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 354 Issue: 3
  • Publication Date: 2021
  • Doi Number: 10.1002/ardp.202000273
  • Journal Name: ARCHIV DER PHARMAZIE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database, Index Chemicus (IC)
  • Keywords: chalcone, COX-1/2, cyclooxygenase inhibition, docking, selectivity, ANTIINFLAMMATORY EVALUATION, CYCLOOXYGENASE INHIBITION, ULCEROGENIC LIABILITY, DERIVATIVES, PYRAZOLE, 1,3,5-TRIARYLPYRAZOLINE, ANTICANCER, CELECOXIB, ANALOGS
  • Anadolu University Affiliated: Yes

Abstract

A new series of chalcones (1-9) possessing an SO2CH3 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, H-1 NMR (nuclear magnetic resonance), C-13 NMR, and high-resolution mass spectroscopic methods. Enzyme inhibition studies revealed that most of the compounds showed a moderate-to-strong inhibitory activity (IC50 = 0.18-0.34 mu M) against the COX-2 enzyme as compared with celecoxib (IC50 = 0.12 mu M), ibuprofen (IC50 = 5.33 mu M), and nimesulide (IC50 = 1.68 mu M). 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 IC50 values of 0.21, 0.19, and 0.18 mu M, 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.