Background: α-Glucosidase inhibitors have occupied a significant position in the treatment of type 2 diabetes. In
this respect, development of novel and efficient non sugar-based inhibitors are highly in demand.
Objective: Design and synthesis of new 5-arylisoxazole-1,3,4-thiadiazole hybrids possessing α-glucosidase inhibitory activity was 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) comparing with acarbose as the reference drug (IC50 = 750.0 µM). Also,
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 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 developments.