Pharmacological screening for anti-inflammatory, analgesic activity of pyrazolyl derivatives along with molecular docking studies

The pyrazole derivatives were synthesized and pharmacologically evaluated for analgesic (tail flick) and anti-inflammatory (based on carrageenan-induced paw edema) activities. Compound 4k showed high potency as an anti-inflammatory agent after 3 and 4-h time intervals (P < 0.001) equipotent to indomethacin. They were devoid of ulcerogenic potential when administered at a dose of 30 mg/kg. The compounds, which showed less ulcerogenic action, also showed reduced malondialdehyde content (MDA), which is one of the byproduct of lipid peroxidation. Further docking studies of titled compounds was done to understand key interactions responsible for observed inhibition of COX enzyme. The most active compound 4k was found to have −11.192 kcal/mol, as the free energy of binding. Various other key interactions between the synthesized molecules and active site of COX-2 enzyme, responsible for the obtained pharmacological results were also reported. Most of the active compounds were docked well into the active sites of the receptor.