Synthesis, Molecular Docking and α-Glucosidase Inhibitory Activity Study of 2,4,6-triaryl Pyrimidine Derivatives

Author(s): Mohammed Hussen Bule, Roghaieh Esfandyari, Tadesse Bekele Tafesse, Mohsen Amini*, Mohammad Ali Faramarzi, Mohammad Abdollahi

Journal Name: Letters in Drug Design & Discovery

Volume 17 , Issue 10 , 2020

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Graphical Abstract:


Background: α-Glucosidase inhibitors hinder the carbohydrate digestion and play an important role in the treatment of diabetes mellitus. α-glucosidase inhibitors available on the market are acarbose, miglitol, and voglibose. However, the use of acarbose is diminishing due to related side effects like diarrhea, bloating and abdominal distension.

Objectives: This study aimed to synthesize 2,4,6-triaryl pyrimidines derivatives, screen their α- glucosidase inhibitory activity, perform kinetic and molecular docking studies.

Methods: A series of 2,4,6-triaryl pyrimidine derivatives were synthesized and their α-glucosidase inhibitory activity was screened in vitro. Pyrimidine derivatives 4a-m were synthesized via a twostep reaction with a yield between 49 and 93%. The structure of the synthesized compounds was confirmed by different spectroscopic techniques (IR, NMR and MS). The in vitro α-glucosidase inhibition activities of the synthesized compounds 4a-m was also evaluated against Saccharomyces cerevisiae α-glucosidase.

Results and Discussion: The majority of synthesized compounds had α-glucosidase inhibitory activity. Particularly compounds 4b and 4g were the most active compounds with an IC50 value of 125.2± 7.2 and 139.8 ± 8.1 μM respectively. The kinetic study performed for the most active compound 4b revealed that the compound was a competitive inhibitor of Saccharomyces cerevisiae α-glucosidase with Ki of 122 μM. The molecular docking study also revealed that the two compounds have important binding interactions with the enzyme active site.

Conclusion: 2,4,6-triarylpyrimidine derivative 4a-m were synthesized and screened for α- glucosidase inhibitory activity. Most of the synthesized compounds possess α-glucosidase inhibitory activity, and compound 4b demonstrated the most significant inhibitory action as compared to acarbose.

Keywords: α-glucosidase inhibitor, pyrimidine, synthesis, enzyme assay, kinetic study, docking.

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Article Details

Year: 2020
Published on: 11 October, 2020
Page: [1216 - 1226]
Pages: 11
DOI: 10.2174/1570180817666200103130536
Price: $65

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