Design and Synthesis of Novel 5-Arylisoxazole-1,3,4-thiadiazole Hybrids as α-Glucosidase Inhibitors

(E-pub Ahead of Print)

Author(s): Mina Saeedi, Azadeh Eslami, Seyedeh Sara Mirfazli, Mahsa Zardkanlou, Mohammad Ali Faramarzi, Mohammad Mahdavi, Tahmineh Akbarzadeh*

Journal Name: Letters in Drug Design & Discovery

Become EABM
Become Reviewer
Call for Editor


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.

Keywords: 5-Arylisoxazole, Docking, α-Glucosidase, Kinetic study, 1, 3, 4-Thiadiazole, Synthesis

Rights & PermissionsPrintExport Cite as

Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1570180817999201104125018
Price: $95