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
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