Salicylic acid is an NSAID with serious side effects on the GIS. The side effects of salicylic acid on the GIS are slightly reduced by acetylating salicylic acid. 12 new ester analogs of salicylic acid were synthesized with high yields in this study. The chemical structures of the synthesized compounds were characterized by 1 H-NMR, 13 C-NMR, and HRMS spectra. The inhibitory potential of the compounds was evaluated on COXs by in vitro and in silico studies. The COX2 inhibitory activity of the most potent inhibitor MEST1 (IC50 : 0.048 μM) was found to be much higher than the COX2 inhibitory activity of aspirin (IC50 : 2.60 μM). In docking studies, the strongest inhibitor among the compounds synthesized was predicted to be MEST1, with the lowest binding energy. Docking studies revealed that MEST1 extends from the hydrophobic channel to the top of the cyclooxygenase active site, forming various interactions with residues in the binding pocket.
Keywords: COXs; Synthesis; molecular docking; salicylates.
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