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Study on the Interaction of 1,5-Diaryl Pyrrole Derivatives With Αglucosidase; Synthesis, Molecular Docking, and Kinetic Study Publisher Pubmed



Tafesse TB1, 2, 3 ; Moghadam ES2 ; Bule MH1, 2, 4 ; Faramarzi MA5 ; Abdollahi M6 ; Amini M2
Authors
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Authors Affiliations
  1. 1. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences-International Campus (IC-TUMS), Tehran, Iran
  2. 2. Department of Medicinal Chemistry, Faculty of Pharmacy, Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
  3. 3. School of Pharmacy, College of Health & Medical Sciences, Haramaya University, Harar, Ethiopia
  4. 4. Department of Pharmacy, College of Medicine and Health Sciences, Ambo University, Ambo, Ethiopia
  5. 5. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, The Institute of Pharmaceutical Sciences, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Pharmacology and Toxicology, Faculty of Pharmacy and The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran

Source: Medicinal Chemistry Published:2021


Abstract

Background: The delaying of absorption of glucose is one of the principal therapeutic approaches of type 2 diabetes. α-glucosidase inhibitors compete with the α-glucosidase enzyme activity, which helps to reduce the conversion of carbohydrates into glucose and thereby control the postprandial hyperglycemia incidence. Objective: The aim of this study was to synthesize a series of novel 1,5-diphenyl pyrrole derivatives and evaluate their in vitro α-glucosidase inhibitory activities. Methods: Compounds were synthesized through a multistep reaction and were evaluated for αglucosidase inhibitory activities. Molecular docking and kinetic studies were carried out to predict the mode of binding and mechanism of inhibition for the most active compounds, 5g and 5b, against α-glucosidase. Results: Synthesized compounds showed good in vitro α-glucosidase inhibitory activity with IC50 values in the range of (117.5 ± 3.8 to 426.0 ± 10.2 µM) as compared to acarbose, the standard drug, (750 ± 8.7 µM). Compound 5g (117.5 ± 3.8 µM) ascertained as the most potent inhibitor of α-glucosidase in a competitive mode. The binding energies of compounds 5g and 5b (119.0 ± 7.5 µM), as observed from the best docking conformations, indicate that they have a lower free binding energy (-3.26 kcal/mol and-3.0 kcal/mol, respectively) than acarbose (2.47 kcal/mol). Conclusion: The results of our study revealed that the synthesized compounds are a potential candidate for α-glucosidase inhibitors for the management of postprandial hyperglycemia for further investigation. © 2021 Bentham Science Publishers.
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