In vitro and in silico studies on novel N-substituted-3,5-diaryl-pyrazoline derivatives as COX-2 inhibitors and anti-inflammatory agents

Abstract

The presence of a reactive ?,?-unsaturated keto group along with substituted aryl ring improves biological profile of pyrazoline nucleus. Considering this fact a study was planned to synthesize novel pyrazoline derivatives incorporated with chalcone backbone and their evaluation as COX-2 inhibitors and anti-inflammatory agents. Bovine serum albumin denaturation assay was used to measure in vitro anti-inflammatory activity. Molecular docking study was performed using Schrödinger-Maestro 9.0 molecular docking software and cyclooxygenase-2 (COX-II) receptor PDB ID: 4-COX. Some of the synthesized compounds showed remarkable anti-inflammatory potential. The compound (E)-3-(4-hydroxyphenyl)-1-(3-(4-hydroxyphenyl)-5-phenyl-4,5-dihydropyrazol-1-yl)prop-2-en-1-one 6d was found to be the most potent anti-inflammatory agents with 69.88% inhibition of protein denaturation. The outcome of docking study also supported results of in vitro anti-inflammatory activity and docking score for compound 6d was found to be 6.70379 which was comparable to the co-crystallized ligand. The results reveal that the synthesized compound can serve as potential lead for the development of novel anti-inflammatory agents.