Analgesic Activity of Acyl-Salicylic Acid Derivatives And In Silico Docking Study For Their Potency As Cyclooxygenase-2 Inhibitors

A series of acyl salicylic acid derivatives were screened to investigate their analgesic activities and their potency as cyclooxygenase-2 (COX-2) inhibitors. Fourteen compounds (BS1–14) were assayed by acetic acid induced writhing test. Their ability for interaction with COX-2 was studied through a docking simulation at the COX-2 active site (PDB. 5IKQ). The results of the analgesic activity test gave 3 compounds that produce ED 50 < 0.39 mmol/kg body weight, lower than aspirin as a positive control. The compounds  BS3  and  BS4  showed excellent analgesic activity and the tert -butyl substituted molecule  BS3  ( O -(4- tert -butylbenzoyl)-salicylic acid analog) showed the highest analgesic activity with ED 50 of 0.26 mmol/kg. Based on in silico molecular docking, it is known that almost all of the tested ligands (12 compounds) showed a higher binding affinity for COX-2 than meclofenamic acid which is a COX-2 inhibitory NSAID. The results of  in vivo analgesic activity were justified with the outcome of  in silico  investigation. Molecular docking of acyl-salicylates confirmed in vivo experiments and it was found that BS3 was the most active compound as an analgesic agent and the most potent as a COX-2 inhibitor among the evaluated compounds. a