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Cyanoacetohydrazide Linked to 1,2,3-Triazole Derivatives: A New Class of Α-Glucosidase Inhibitors Publisher Pubmed



Iraji A1, 2 ; Shareghibrojeni D3 ; Mojtabavi S4 ; Faramarzi MA4 ; Akbarzadeh T3, 5 ; Saeedi M5, 6
Authors
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Authors Affiliations
  1. 1. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  2. 2. Central Research Laboratory, Shiraz University of Medical Sciences, Shiraz, Iran
  3. 3. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, 1417614411, Iran
  5. 5. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: Scientific Reports Published:2022


Abstract

In this work, a novel series of cyanoacetohydrazide linked to 1,2,3-triazoles (9a–n) were designed and synthesized to be evaluated for their anti-α-glucosidase activity, focusing on the fact that α-glucosidase inhibitors have played a significant role in the management of type 2 diabetes mellitus. All synthesized compounds except 9a exhibited excellent inhibitory potential, with IC50 values ranging from 1.00 ± 0.01 to 271.17 ± 0.30 μM when compared to the standard drug acarbose (IC50 = 754.1 ± 0.5 μM). The kinetic binding study indicated that the most active derivatives 9b (IC50 = 1.50 ± 0.01 μM) and 9e (IC50 = 1.00 ± 0.01 μM) behaved as the uncompetitive inhibitors of α-glucosidase with Ki = 0.43 and 0.24 μM, respectively. Moreover, fluorescence measurements were conducted to show conformational changes of the enzyme after binding of the most potent inhibitor (9e). Calculation of standard enthalpy (ΔHm°) and entropy (ΔSm°) values confirmed the construction of hydrophobic interactions between 9e and the enzyme. Also, docking studies indicated desired interactions with important residues of the enzyme which rationalized the in vitro results. © 2022, The Author(s).
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