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

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

Volume 18 , Issue 5 , 2021

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Graphical Abstract:


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 developments.

Keywords: 5-Arylisoxazole, docking, α-glucosidase, kinetic study, 1, 3, 4-thiadiazole, synthesis.

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Article Details

Year: 2021
Published on: 04 November, 2020
Page: [436 - 444]
Pages: 9
DOI: 10.2174/1570180817999201104125018
Price: $65

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