Background: α-Glucosidase inhibitors have occupied a significant position in the treatment
of type 2 diabetes. In this respect, the development of novel and efficient non-sugar-based
inhibitors is in high demand.
Objective: Design and synthesis of new 5-arylisoxazole-1,3,4-thiadiazole hybrids possessing α-
glucosidase inhibitory activity were developed.
Methods: Different derivatives were synthesized by the reaction of various 5-arylisoxazole-3-
carboxylic acids and ethyl 2-((5-amino-1,3,4-thiadiazol-2-yl)thio)acetate. Finally, they were evaluated
for their α-glucosidase inhibitory activity.
Results: It was found that ethyl 2-((5-(5-(2-chlorophenyl)isoxazole-3-carboxamido)-1,3,4-thiadiazol-
2-yl)thio)acetate (5j) was the most potent compound (IC50 = 180.1 μM) compared with acarbose as
the reference drug (IC50 = 750.0 μM). Also, the kinetic study of 5j revealed a competitive inhibition
and docking study results indicated desired interactions of that compound with amino acid residues
located close to the active site of α-glucosidase.
Conclusion: Good α-glucosidase inhibitory activity obtained by the title compounds introduced
them as an efficient scaffold, which merits to be considered in anti-diabetic drug discovery