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Study on the interaction of triaryl-dihydro-1,2,4-oxadiazoles with α-glucosidase

  • Arefeh Khosravi
  • Gholamhassan VaeziEmail author
  • Vida Hojati
  • Khosrou AbdiEmail author
Research article
  • 14 Downloads

Abstract

Purpose

One of the therapeutic approaches in the management of Type 2 diabetes is delaying the absorption of glucose through α-glucosidase enzymes inhibition, which can reduce the incidence of postprandial hyperglycemia. The existence of chronic postprandial hyperglycemia impaired the endogenous antioxidant defense due to inducing oxidative stress induced pancreatic β-cell destruction through uncontrolled free radicals generation such as ROS, which in turn, leads to various macrovascular and microvascular complications. This study aimed to synthesize 2-aryl-4,6-diarylpyrimidine derivatives, screen their α-glucosidase inhibitory activity, perform kinetic and molecular docking studies.

Methods

A series of 3,4,5-triphenyl-4,5-dihydro-1,2,4-oxadiazole derivatives were synthesized and their α-glucosidase inhibitory activity was screened in vitro. Compounds 6a-k were synthesized via a two-step reaction with a yield between 65 and 88%. The structural elucidation of the synthesized derivatives was performed by different spectroscopic techniques. α-Glucosidase inhibitory activity of the oxadiazole derivatives 6a-k was evaluated against Saccharomyces cerevisiae α-glucosidase.

Results

Most of the synthesized compounds demonstrated α-glucosidase inhibitory action. Particularly compounds 6c, 6d and 6 k were the most active compounds with IC50 values 215 ± 3, 256 ± 3, and 295 ± 4 μM respectively. A kinetic study performed for compound 6c revealed that the compound is a competitive inhibitor of Saccharomyces cerevisiae α-glucosidase with Ki of 122 μM. The docking study also revealed that the two compounds, 6c and 6 k, have important binding interactions with the enzyme active site.

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 the postprandial hyperglycemia incidence.

Graphical abstract

Keywords

1,2,4-oxadiazoles α-Glucosidase activity Docking Kinetic study 

Notes

Acknowledgements

The authors would like to express their thankfulness to Tehran University of Medical Sciences for providing the research data facilities.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

40199_2019_322_MOESM1_ESM.pdf (2.8 mb)
ESM 1 (PDF 2861 kb)

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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of BiologyDamghan branch, Islamic Azad UniversityDamghanIran
  2. 2.Department of ChemistryIslamic Azad University, North Tehran BranchTehranIran
  3. 3.Department of Medicinal Chemistry and RadiopharmacyTehran University of Medical Sciences TehranIran

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