Synthesis, evaluation and docking studies on 3-alkoxy-4-methanesulfonamido acetophenone derivatives as non ulcerogenic anti-inflammatory agents

A series of 3-alkoxy-4-methanesulfonamido acetophenone derivatives were synthesized and evaluated for their anti-inflammatory activity in carrageenan-induced rat paw edema model. The synthesized compounds were also investigated for their gastric ulcerogenic potential. The compounds 4a, 4c and 4d showed comparable anti-inflammatory activity to rofecoxib and indomethacin, the standard drugs taken in both studies and were also non ulcerogenic at the test doses. In silico (docking studies) were done to investigate the hypothetical binding mode of the target compounds to the cyclooxygenase isoenzyme (COX-2). A binding model has been proposed based on the docking studies. Selected physicochemical properties were calculated for theoretical ADME profiling of the compounds and excellent compliance was shown with Lipinski’s rules.

Graphical abstractA series of 3-alkoxy-4-methanesulfonamido acetophenone derivatives have been synthesized as non ulcerogenic anti-inflammatory agents. A binding model has been proposed based on in silico (docking studies) with the cyclooxygenase isoenzyme (COX-2).Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Anti-inflammatory activity of 3-alkoxy-4-methanesulfonamido acetophenone derivatives. ► In vivo studies show no ulcerogenic potential at the test doses. ► Hypothetical binding model for COX-2 binding through in silico (docking studies). ► Compliance with lipinski’s rules signifies good potential for oral bioavailability.