New 4-(arylidene)amino-1,2,4-traizole-5-thiol derivatives and their acyclo thioglycosides as α-glucosidase and α-amylase inhibitors: Design, synthesis, and molecular modelling studies

Abstract

A series of 1,2,4-triazole Schiff`s bases 3-9 and their respective acyclo thioglycosides 10-15 based α-glucosidase and α-amylase inhibitors were synthesized under conventional and ultrasound irradiation, respectively. All derivatives were evaluated for their inhibitory activity against α-glucosidase and α-amylase enzymes. All the synthesized compounds exhibited excellent inhibitory activities against both enzymes (IC50= 1.65- 5.78 µM and 1.49-5.81 µM for α-amylase and α-glucosidase, respectively) compared with the standard drug acarbose (IC50= 18.71 µM and 19.51 µM for α-amylase and α-glucosidase, respectively). The most promising derivatives are those with 4-hydroxy, 4-methoxy and 4-dimethylamino phenyl groups 7, 13, 8, 14 and 5, 11, respectively. The acyclo thioglycosides 10-15 showed lower inhibition compared with the thiol derivatives 3-9. Further structure activity relationship data revealed that the imine and the thiol groups critically control potency. The kinetics of α-amylase and α-glucosidase inhibition by the most potent derivatives 7 and 8 were assayed, where a competitive type of inhibition was concluded. Molecular docking study predicted the possible binding interaction of the most potent compounds with the enzymes and justified the design rationale.