Design and Synthesis of Novel 5-Arylisoxazole-1,3,4-Thiadiazole Hybrids As Α-Glucosidase Inhibitors

Design and Synthesis of Novel 5-Arylisoxazole-1,3,4-Thiadiazole Hybrids As Α-Glucosidase Inhibitors Publisher

Saeedi M^{1, 2} ; Eslami A³ ; Mirfazli SS⁴ ; Zardkanlou M⁵ ; Faramarzi MA⁵ ; Mahdavi M⁶ ; Akbarzadeh T^{2, 3}

Show Affiliations

1. Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
2. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran
3. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
4. Department of Medicinal Chemistry, School of Pharmacy-International Campus, Iran University of Medical Sciences, Tehran, Iran
5. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, 1417614411, Iran
6. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: Letters in Drug Design and Discovery Published:2021

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 evalu-ated 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. ©2021 Bentham Science Publishers.

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Style	Citing Format
MLA	Saeedi M, et al.. "Design and Synthesis of Novel 5-Arylisoxazole-1,3,4-Thiadiazole Hybrids As Α-Glucosidase Inhibitors." Letters in Drug Design and Discovery, vol. 18, no. 5, 2021, pp. 436-444.
APA	Saeedi M, Eslami A, Mirfazli SS, Zardkanlou M, Faramarzi MA, Mahdavi M, Akbarzadeh T (2021). Design and Synthesis of Novel 5-Arylisoxazole-1,3,4-Thiadiazole Hybrids As Α-Glucosidase Inhibitors. Letters in Drug Design and Discovery, 18(5), 436-444.
Chicago	Saeedi M, Eslami A, Mirfazli SS, Zardkanlou M, Faramarzi MA, Mahdavi M, Akbarzadeh T. "Design and Synthesis of Novel 5-Arylisoxazole-1,3,4-Thiadiazole Hybrids As Α-Glucosidase Inhibitors." Letters in Drug Design and Discovery 18, no. 5 (2021): 436-444.
Harvard	Saeedi M et al. (2021) 'Design and Synthesis of Novel 5-Arylisoxazole-1,3,4-Thiadiazole Hybrids As Α-Glucosidase Inhibitors', Letters in Drug Design and Discovery, 18(5), pp. 436-444.
Vancouver	Saeedi M, Eslami A, Mirfazli SS, Zardkanlou M, Faramarzi MA, Mahdavi M, et al.. Design and Synthesis of Novel 5-Arylisoxazole-1,3,4-Thiadiazole Hybrids As Α-Glucosidase Inhibitors. Letters in Drug Design and Discovery. 2021;18(5):436-444.
BibTex	@article{ author = {Saeedi M and Eslami A and Mirfazli SS and Zardkanlou M and Faramarzi MA and Mahdavi M and Akbarzadeh T}, title = {Design and Synthesis of Novel 5-Arylisoxazole-1,3,4-Thiadiazole Hybrids As Α-Glucosidase Inhibitors}, journal = {Letters in Drug Design and Discovery}, volume = {18}, number = {5}, pages = {436-444}, year = {2021} }
RIS	TY - JOUR AU - Saeedi M AU - Eslami A AU - Mirfazli SS AU - Zardkanlou M AU - Faramarzi MA AU - Mahdavi M AU - Akbarzadeh T TI - Design and Synthesis of Novel 5-Arylisoxazole-1,3,4-Thiadiazole Hybrids As Α-Glucosidase Inhibitors JO - Letters in Drug Design and Discovery VL - 18 IS - 5 SP - 436 EP - 444 PY - 2021 ER -

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