Background: Results of our previous studies on antiglycation activity, and the non-cytotoxicity of 2-mercapto benzothiazoles, prompted us to further widen our investigation towards the identification of leads against diabetes mellitus.
Method: 33 derivatives of 2-mercapto benzothiazoles 1-33 were evaluated for in vitro α-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 α-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 α-glucosidase inhibitory activity in the range of IC50 = 31.21-208.63 μM, as compared to the standard drug acarbose (IC50 = 875.75 ± 2.08 μM). 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 μM.
Conclusion: A number of compounds were identified as dual nature as antiglycating agent, and α-glucosidase inhibitors. These compounds may serve as potential lead candidates for the management of diabetes mellitus.