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Medicinal Chemistry


ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Research Article

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*

Volume 17, Issue 5, 2021

Published on: 06 December, 2019

Page: [545 - 553] Pages: 9

DOI: 10.2174/1573406415666191206100336

Price: $65


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, 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.

Keywords: α-Glucosidase activity, docking, kinetic study, synthesis, pyrrole, diabetes.

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