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., ...Daha Fazla

ARCHIV DER PHARMAZIE, cilt.354, sa.3, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 354 Sayı: 3
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1002/ardp.202000273
  • Dergi Adı: ARCHIV DER PHARMAZIE
  • Derginin Tarandığı İndeksler: 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)
  • Anahtar Kelimeler: chalcone, COX-1/2, cyclooxygenase inhibition, docking, selectivity, ANTIINFLAMMATORY EVALUATION, CYCLOOXYGENASE INHIBITION, ULCEROGENIC LIABILITY, DERIVATIVES, PYRAZOLE, 1,3,5-TRIARYLPYRAZOLINE, ANTICANCER, CELECOXIB, ANALOGS
  • Anadolu Üniversitesi Adresli: Evet

Özet

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.