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Synthesis and biological evaluation of 2-(2-methyl-1H-pyrrol-3-yl)-2-oxo-N-(pyridine-3-yl) acetamide derivatives: in vitro α-glucosidase inhibition, and kinetic and molecular docking study

  • Tadesse Bekele Tafesse
  • Ebrahim Saeedian Moghadam
  • Mohammed Hussen Bule
  • Neda Abadian
  • Mohammad Abdollahi
  • Mohammad Ali FaramarziEmail author
  • Mohsen AminiEmail author
Original Paper
  • 13 Downloads

Abstract

One of the therapeutic approaches in the management of type 2 diabetes is delaying the glucose absorption through α-glucosidase enzyme inhibition, which can reduce the occurrence of postprandial hyperglycemia. Based on this thought, a series of novel chloro-substituted 2-(2-methyl-1-phenyl-1H-pyrrol-3-yl)-2-oxo-N-(pyridin-3-yl) acetamide derivatives 5ai were synthesized and their α-glucosidase inhibitory activities were evaluated. All the synthesized compounds have shown moderate to excellent in vitro α-glucosidase inhibitory activity with IC50 values in the range of 111–673 µM) as compared to acarbose, the standard drug (750 ± 9 µM). Compound 5e (111 ± 12 µM), among the series, was the most potent inhibitor of α-glucosidase in a competitive mode of action based on the kinetic study. The molecular docking study of compounds 5e and 5a revealed that they have a lower free binding energy (− 4.27 kcal/mol and − 3.17 kcal/mol, respectively) than acarbose (− 2.47 kcal/mol), which indicates that the target compound binds more easily to the enzyme than acarbose does. The outcomes from the molecular docking studies supported the results obtained from the in vitro assay. In conclusion, the overall results of our study reveal that the synthesized compounds could be a potential candidate in the search for novel α-glucosidase inhibitors to manage postprandial hyperglycemia incidence.

Keywords

α-Glucosidase activity Docking Kinetic study Synthesis Pyrrole 

Notes

Acknowledgements

This research was supported by a grant from Tehran University of Medical Sciences (GN: 39750).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11696_2019_999_MOESM1_ESM.pdf (834 kb)
Supplementary material 1 (PDF 833 kb)

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Copyright information

© Institute of Chemistry, Slovak Academy of Sciences 2019

Authors and Affiliations

  • Tadesse Bekele Tafesse
    • 1
    • 2
    • 3
  • Ebrahim Saeedian Moghadam
    • 2
  • Mohammed Hussen Bule
    • 1
    • 2
    • 4
  • Neda Abadian
    • 5
  • Mohammad Abdollahi
    • 6
  • Mohammad Ali Faramarzi
    • 5
    Email author
  • Mohsen Amini
    • 2
    Email author
  1. 1.Department of Medicinal Chemistry, Faculty of PharmacyTehran University of Medical Sciences-International Campus (IC-TUMS)TehranIran
  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 SciencesTehranIran
  3. 3.School of Pharmacy, College of Health & Medical SciencesHaramaya UniversityHararEthiopia
  4. 4.Department of Pharmacy, College of Medicine and Health SciencesAmbo UniversityAmboEthiopia
  5. 5.Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and The Institute of Pharmaceutical SciencesTehran University of Medical SciencesTehranIran
  6. 6.Department of Pharmacology and Toxicology, Faculty of Pharmacy and The Institute of Pharmaceutical SciencesTehran University of Medical SciencesTehranIran

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