Effective ?-glycosidase inhibitors based on polyphenolic benzothiazole heterocycles

Abstract

alpha-Glycosidase inhibition is one of the main approaches to treat Diabetes mellitus. Polyphenolic moieties are known to be responsible for yielding exhibit potent alpha-glycosidase inhibitory effects. In addition, compounds containing benzothiazole and Schiff base functionalities were previously reported to show alpha-glycosidase inhibition. In this paper, the synthesis of seven new phloroglucinol-containing benzothiazole Schiff base derivatives through the reaction of 6-substituted-2-aminobenzothiazole compounds with 2,4,6-trihydroxybenzaldehyde using acetic acid as a catalyst was reported. The synthesized compounds were characterized using spectroscopic methods such as FT-IR, 1 H NMR, 13 C NMR, and elemental analysis. The synthesized compounds were evaluated for their inhibitory effects on alpha-glycosidase, compounds 3f and 3g were found to show significant inhibitory properties when compared to the positive control. The IC 50 values of 3f and 3g were calculated as 24.05 +/- 2.28 and 18.51 +/- 1.19 mu M, respectively. Kinetic studies revealed that compounds 3f and 3g exhibited uncompetitive mode of inhibition against alpha-glycosidase. Molecular modeling predicted druglikeness for the title compounds and underpinned the importance of phloroglucinol hydroxyls for interacting with the key residues of alpha-glycosidase.