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2-Mercapto Benzothiazole Derivatives: As Potential Leads for the Diabetic Management
Saeed Ullah1, Salma Mirza1, Uzma Salar2
1H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
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 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.
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