Methanesulfonamide derivatives as gastric safe anti-inflammatory agents: Design, synthesis, selective COX-2 inhibitory activity, histopathological and histochemical studies

Novel chalcone 3a-c, pyrazoline 4a-i and pyridine 5a-c, 6a & b derivatives bearing methanesulfonamide moiety were synthesized. Their construction was confirmed using spectral data and elemental analysis. The stereochemical configuration for compounds 3a-c was predicted by MM2 property and 1H NMR spectra. All the prepared compounds were screened for their in vitro COX-1/COX-2 inhibitory activities and in vivo antiinflammatory activity. The most active anti-inflammatory derivatives, 4f-4i, after 3, 5 & 7 h were further subjected to histopathological and histochemical studies showing safe effect on gastric mucosa, especially 4h derivative. To explore the mechanism of action of COX-2 inhibitory compounds 4f and 6b with the highest S.I. values, they were docked inside COX-2 active site. Physicochemical properties for 4f-i and 6b derivatives were predicted and compared to the reference drug celecoxib. They showed good oral bio-availability specially pyrazoline derivative 4f and pyridine containing compound 6b.