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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
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Authors Affiliations
  1. 1. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Pharmacy, College of Medicine and Health Sciences, Ambo University, Ambo, Ethiopia
  4. 4. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Iran
  5. 5. School of Pharmacy, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia

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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