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Design, Synthesis, in Vitro Anti-Α-Glucosidase Evaluations, and Computational Studies of New Phthalimide-Phenoxy-1,2,3-Triazole-N-Phenyl (Or Benzyl) Acetamides As Potential Anti-Diabetic Agents Publisher Pubmed



Emadi M1 ; Halimi M2 ; Moazzam A3 ; Hosseini S4 ; Mojtabavi S5 ; Faramarzi MA5 ; Ghadimi R6 ; Moghadamnia AA7, 8 ; Nasliesfahani E9 ; Mohammadikhanaposhtani M8 ; Mahdavi M3
Authors
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Authors Affiliations
  1. 1. Electrical and Computer Engineering Department, Babol Noshirvani University of Technology, Babol, Iran
  2. 2. Department of Biology, Babol Branch, Islamic Azad University, Babol, Iran
  3. 3. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Shahid Beheshti University of Medical Sciences, Tehran, Iran
  5. 5. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Social Determinants of Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
  7. 7. Department of Pharmacology and Toxicology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
  8. 8. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
  9. 9. Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: Scientific Reports Published:2023


Abstract

An important target in the treatment of type 2 diabetes is α-glucosidase. Inhibition of this enzyme led to delay in glucose absorption and decrease in postprandial hyperglycemia. A new series of phthalimide-phenoxy-1,2,3-triazole-N-phenyl (or benzyl) acetamides 11a–n were designed based on the reported potent α-glucosidase inhibitors. These compounds were synthesized and screened for their in vitro inhibitory activity against the latter enzyme. The majority of the evaluated compounds displayed high inhibition effects (IC50 values in the range of 45.26 ± 0.03–491.68 ± 0.11 µM) as compared to the positive control acarbose (IC50 value = 750.1 ± 0.23 µM). Among this series, compounds 11j and 11i represented the most potent α-glucosidase inhibitory activities with IC50 values of 45.26 ± 0.03 and 46.25 ± 0.89 µM. Kinetic analysis revealed that the compound 11j is a competitive inhibitor with a Ki of 50.4 µM. Furthermore, the binding interactions of the most potent compounds in α-glucosidase active site were studied through molecular docking and molecular dynamics. The latter studies confirmed the obtained results through in vitro experiments. Furthermore, in silico pharmacokinetic study of the most potent compounds was also performed. © 2023, The Author(s).
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