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Synthesis, in Vitro and in Silico Enzymatic Inhibition Assays, and Toxicity Evaluations of New 4,5-Diphenylimidazole-N-Phenylacetamide Derivatives As Potent Α-Glucosidase Inhibitors Publisher



Mohammadikhanaposhtani M1 ; Nikraftar A2 ; Asgari MS3 ; Emadi M4 ; Mojtabavi S5 ; Faramarzi MA5 ; Rastegar H6 ; Larijani B7 ; Mahdavi M7
Authors
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Authors Affiliations
  1. 1. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
  2. 2. Department of Medicinal Chemistry, Faculty of Pharmacy, Islamic Azad University, Ayatollah Amoli Branch, Amol, Iran
  3. 3. School of Chemistry, College of Science, University of Tehran, Tehran, Iran
  4. 4. Electrical and Computer Engineering Department, Babol Noshirvani University of Technology, Babol, Iran
  5. 5. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Cosmetic Products Research Center, Iranian Food and Drug Administration, MOHE, Tehran, Iran
  7. 7. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: Medicinal Chemistry Research Published:2021


Abstract

α-Glucosidase is responsible for glucose release of oligosaccharides and disaccharides in the intestine and increase postprandial hyperglycemia. Inhibition of this enzyme is a beneficial therapeutic method for glycemic control in diabetes. This study deals with the design and synthesis of 4,5-diphenylimidazole-N-phenylacetamide derivatives 7a–l and the screen of these compounds for their potential for α-glucosidase inhibition. All the synthesized compounds exhibited superior α-glucosidase inhibition (IC50 = 90.0–598.5 µM) as compared to standard inhibitor acarbose (IC50 = 750.0 µM). In contrast, these compounds were inactive against α-amylase. Among the synthesized compounds, compound 7h was the most potent inhibitor of this library and was a competitive inhibitor into α-glucosidase with Ki value = 86.3 μM. Docking study of the most potent compounds was performed to evaluate the binding interactions of these compounds with the active site of enzyme and to determine of binding energies of ligand–enzyme complexes. The results of this in silico study are in complete agreement with the results obtained from in vitro α-glucosidase inhibition assay. Docking study of the most potent compound demonstrated that it interacted with important residues in the active site of α-glucosidase. In vitro cytotoxic activity of the most potent compounds and in silico druglikeness/ADME/toxicity study of these compounds were evaluated. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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