Quinazolinone-1,2,3-Triazole-Acetamide Conjugates As Potent Α-Glucosidase Inhibitors: Synthesis, Enzyme Inhibition, Kinetic Analysis, and Molecular Docking Study

Quinazolinone-1,2,3-Triazole-Acetamide Conjugates As Potent Α-Glucosidase Inhibitors: Synthesis, Enzyme Inhibition, Kinetic Analysis, and Molecular Docking Study Publisher

Moghadam Farid S¹ ; Iraji A^{2, 3} ; Mojtabavi S⁴ ; Ghasemi M⁵ ; Faramarzi MA⁴ ; Mahdavi M¹ ; Barazandeh Tehrani M⁵ ; Akbarzadeh T^{5, 6} ; Saeedi M^{6, 7}

Show Affiliations

1. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
2. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
3. Central Research Laboratory, Shiraz University of Medical Sciences, Shiraz, Iran
4. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, 1417614411, Iran
5. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
6. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran
7. Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: RSC Medicinal Chemistry Published:2023

Abstract

In this study, new hybrids of quinazolinone-1,2,3-triazole-acetamide were designed, synthesized, and screened for their α-glucosidase inhibitory activity. The results obtained from the in vitro screening indicated that all analogs exhibited significant inhibitory activity against α-glucosidase (IC50 values ranging from 4.8-140.2 μM) in comparison to acarbose (IC50 = 750.0 μM). The limited structure-activity relationships suggested the variation in the inhibitory activities of the compounds affected by different substitutions on the aryl moiety. The enzyme kinetic studies of the most potent compound 9c, revealed that it inhibited α-glucosidase in a competitive mode with a Ki value of 4.8 μM. In addition, molecular docking studies investigated the structural perturbation and behavior of all derivatives inside the α-glucosidase active site. Next, molecular dynamic simulations of the most potent compound 9c, were performed to study the behavior of the 9c-complex during the time. The results showed that these compounds can be considered as potential antidiabetic agents. © 2023 RSC.

Style	Citing Format
MLA	Moghadam Farid S, et al.. "Quinazolinone-1,2,3-Triazole-Acetamide Conjugates As Potent Α-Glucosidase Inhibitors: Synthesis, Enzyme Inhibition, Kinetic Analysis, and Molecular Docking Study." RSC Medicinal Chemistry, vol. 14, no. 3, 2023, pp. 520-533.
APA	Moghadam Farid S, Iraji A, Mojtabavi S, Ghasemi M, Faramarzi MA, Mahdavi M, Barazandeh Tehrani M, Akbarzadeh T, Saeedi M (2023). Quinazolinone-1,2,3-Triazole-Acetamide Conjugates As Potent Α-Glucosidase Inhibitors: Synthesis, Enzyme Inhibition, Kinetic Analysis, and Molecular Docking Study. RSC Medicinal Chemistry, 14(3), 520-533.
Chicago	Moghadam Farid S, Iraji A, Mojtabavi S, Ghasemi M, Faramarzi MA, Mahdavi M, Barazandeh Tehrani M, Akbarzadeh T, Saeedi M. "Quinazolinone-1,2,3-Triazole-Acetamide Conjugates As Potent Α-Glucosidase Inhibitors: Synthesis, Enzyme Inhibition, Kinetic Analysis, and Molecular Docking Study." RSC Medicinal Chemistry 14, no. 3 (2023): 520-533.
Harvard	Moghadam Farid S et al. (2023) 'Quinazolinone-1,2,3-Triazole-Acetamide Conjugates As Potent Α-Glucosidase Inhibitors: Synthesis, Enzyme Inhibition, Kinetic Analysis, and Molecular Docking Study', RSC Medicinal Chemistry, 14(3), pp. 520-533.
Vancouver	Moghadam Farid S, Iraji A, Mojtabavi S, Ghasemi M, Faramarzi MA, Mahdavi M, et al.. Quinazolinone-1,2,3-Triazole-Acetamide Conjugates As Potent Α-Glucosidase Inhibitors: Synthesis, Enzyme Inhibition, Kinetic Analysis, and Molecular Docking Study. RSC Medicinal Chemistry. 2023;14(3):520-533.
BibTex	@article{ author = {Moghadam Farid S and Iraji A and Mojtabavi S and Ghasemi M and Faramarzi MA and Mahdavi M and Barazandeh Tehrani M and Akbarzadeh T and Saeedi M}, title = {Quinazolinone-1,2,3-Triazole-Acetamide Conjugates As Potent Α-Glucosidase Inhibitors: Synthesis, Enzyme Inhibition, Kinetic Analysis, and Molecular Docking Study}, journal = {RSC Medicinal Chemistry}, volume = {14}, number = {3}, pages = {520-533}, year = {2023} }
RIS	TY - JOUR AU - Moghadam Farid S AU - Iraji A AU - Mojtabavi S AU - Ghasemi M AU - Faramarzi MA AU - Mahdavi M AU - Barazandeh Tehrani M AU - Akbarzadeh T AU - Saeedi M TI - Quinazolinone-1,2,3-Triazole-Acetamide Conjugates As Potent Α-Glucosidase Inhibitors: Synthesis, Enzyme Inhibition, Kinetic Analysis, and Molecular Docking Study JO - RSC Medicinal Chemistry VL - 14 IS - 3 SP - 520 EP - 533 PY - 2023 ER -

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