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Synthesis, Molecular Docking and Α-Glucosidase Inhibitory Activity Study of 2,4,6-Triaryl Pyrimidine Derivatives Publisher



Bule MH1, 2, 3 ; Esfandyari R1 ; Tafesse TB1, 2, 5 ; Amini M1, 2 ; Faramarzi MA2, 4 ; Abdollahi M2, 4
Authors

Source: Letters in Drug Design and Discovery Published:2020


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 two-step 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. © 2020 Bentham Science Publishers.
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