2-Mercapto Benzothiazole Derivatives: As Potential Leads for the Diabetic Management.

Background: Results of our previous studies on antiglycation activity, and the noncytotoxicity of 2-mercapto benzothiazoles, encouraged us to further widen our investigation towards the identification of leads against diabetes mellitus. Methods: 33 derivatives of 2-mercapto benzothiazoles 1-33 were evaluated for in vitro alpha-glucosidase inhibitory activity. Mode of inhibition was deduced by kinetic studies. To predict the interactions of 2-mercapto benzothiazole derivatives 1-33 with the binding pocket of alpha-glucosidase enzyme, molecular docking studies were performed on the selected inhibitors. Results: Compounds 2-4, 6-7, 9-26, 28 and 30 showed many folds potent alpha-glucosidase inhibitory activity in the range of IC50 = 31.21-208.63 mu M, as compared to the standard drug acarbose (IC50 = 875.75 +/- 2.08 mu M). It was important to note that except derivative 28, all other derivatives were also found previously to have antiglycating potential in the range of IC50 = 187.12-707.21 mu M. Conclusion: A number of compounds were identified as dual nature as antiglycating agent and alpha-glucosidase inhibitors. These compounds may serve as potential lead candidates for the management of diabetes mellitus.