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

Arch Pharm (Weinheim). 2021 Mar;354(3):e2000273. doi: 10.1002/ardp.202000273. Epub 2020 Nov 27.

Abstract

A new series of chalcones (1-9) possessing an SO2 CH3 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 (IC50 = 0.18-0.34 μM) against the COX-2 enzyme as compared with celecoxib (IC50 = 0.12 μM), ibuprofen (IC50 = 5.33 μM), and nimesulide (IC50 = 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 IC50 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.

Keywords: COX-1/2; chalcone; cyclooxygenase inhibition; docking; selectivity.

MeSH terms

  • Chalcones / chemical synthesis
  • Chalcones / chemistry
  • Chalcones / pharmacology*
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / chemical synthesis
  • Cyclooxygenase 2 Inhibitors / chemistry
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Humans
  • Molecular Docking Simulation*
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Chalcones
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase 2