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Study on the Interaction of 1,5-diaryl Pyrrole Derivatives with α- glucosidase; Synthesis, Molecular Docking, and Kinetic Study

Author(s):

Tadesse Bekele Tafesse, Ebrahim Saeedian Moghadam, Mohammed Hussen Bule, Mohammad Ali Faramarzi, Mohammad Abdollahi and Mohsen Amini*   Pages 1 - 9 ( 9 )

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 α-glucosidase 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, indicates 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 reveal that the synthesized compounds are a potential candidate for α-glucosidase inhibitors for the management of postprandial hyperglycemia for further investigation.

Keywords:

α-Glucosidase activity, Docking, Kinetic study, Synthesis, Pyrrole, Diabetes

Affiliation:

Department of Medicinal Chemistry, Faculty of Pharmacy, Drug Design and Development Research Center and The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Department of Medicinal Chemistry, Faculty of Pharmacy, Drug Design and Development Research Center and The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Department of Medicinal Chemistry, Faculty of Pharmacy, Drug Design and Development Research Center and The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and The Institute of Pharmaceutical Sciences, Tehran University of Medical Sciences, Tehran, Department of Pharmacology and Toxicology, Faculty of Pharmacy and The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Department of Medicinal Chemistry, Faculty of Pharmacy, Drug Design and Development Research Center and The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran



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