New thiosemicarbazide-1,2,3-triazole hybrids as potent alpha-glucosidase inhibitors: Design, synthesis, and biological evaluation

Abstract

A new series of thiosemicarbazide-1,2,3-triazole hybrids 10a-o has been synthesized, characterized by H-1 NMR, C-13 NMR, and screened for their in vitro alpha-glucosidase inhibitory activity. All of the synthesized compounds displayed excellent alpha-glucosidase inhibitory activity with IC50 values in the range of 75.0 +/- 0.5 to 253.0 +/- 0.5 mu M, as compared to the standard drug acarbose (IC50 = 750.0 +/- 1.5 mu M). Among the synthesized compounds, compound 10h (IC50 = 75.0 +/- 0.5) with 4-methoxy group at phenyl part of thiosemicarbazide moiety and 2,6-dichloro substituents at benzyl moiety was found to be the most potent compound. Kinetic analysis revealed that compound 10h is a competitive inhibitor for alpha-glucosidase. Docking study of compound 10h in the active site of alpha-glucosidase showed that this compound interacted with residues His239, His279, Glu304, Gly306, and Arg312. (C) 2019 Elsevier B.V. All rights reserved.