Synthesis, Biological Evaluation and Molecular Docking of Diarylimidazole Derivatives as New Potential Anti-inflammatory Agents Targeting COX-2 Enzyme.

Abstract

A series of diaryl imidazole derivatives (5a-h) was designed as novel selective COX-2 anti-inflammatory drug candidates. The designed compounds were synthesised, and their structures were characterized by spectroscopic analysis. The anticipated anti-inflammatory activity for the synthesized compounds was assessed by in-vitro cyclooxygenases (COX-1/COX-2) inhibition assay. Most of tested compounds demonstrated moderate COX-2 inhibitory activity and selectivity (IC 50 = 0.068 – 0.80 µm, SI = 7.5 - 175) in comparison to indomethacin (IC 50 = 0.079 µm, SI = 12.5) and celecoxib (IC 50 = 0.046 µm, SI = 315.22). Molecular modelling study of the synthesized compounds into the active site of COX-2 enzyme was performed to rationalize their preferred binding affinity; except for compound 5f , all compounds showed binding with amino acids at the selectivity pocket Additionally, In-silico simulation studies explored the drug drug-likeness parameters of the synthesized compounds, all synthesized compounds exhibited promising physicochemical parameters and pharmacokinetics according to the in-silico simulation results.