New 2-aminobenzothiazole derivatives: Design, synthesis, anti-inflammatory and ulcerogenicity evaluation

Abstract

Two series of twenty diversely substituted benzothiazole amides were designed and synthesized aiming to obtain derivatives with potential anti-inflammatory activity and decreased GIT ulceroginicity. All the synthesized compounds were in-vivo screened for their anti-inflammatory activity using carrageenan induced rat hind paw edema model. Results revealed that compounds 3h and 6a were the most potent ones with remarkable GIT tolerability compared to indomethacin (ED50 = 0.012, 0.016 and 0.015 mmol/kg, respectively). Moreover, compounds 3h and 6a ulcerogenic investigation proved ulcer index= 0 at the first 2 doses (0.01, 0.02 mmol/kg) and surpassing the third dose (0.03 mmol/kg) for 6a only, respectively. In vitro COX-1/COX-2 isozyme selectivity testing revealed the best selectivity index for compound 6a (SI= 3.10) among the investigated compounds compared to celecoxib (SI= 11.89), which was further confirmed with the molecular docking study.