Background: Glucuronidation is essential for the metabolism and excretion of toxic
substances. β-Glucuronidase enzyme slows down the process of glucuronidation, and thus plays an
important role in the on-set of colorectal carcinoma, and many other diseases. Inhibition of β-
glucuronidase activity is thus identified as an important approach for the treatment of several diseases.
Objective: Current study was aimed to synthesize a library of 2-oxo-1,2,3,4-tetrahydropyrimidine
and to evaluate their β-glucuronidase inhibitory activity, and their mode of enzyme inhibition.
Method: We synthesized a series of 2-oxo-1,2,3,4-tetrahydropyrimidines 1-25 by fusing urea,
ethyl acetoacetate, and a variety of aldehydes using copper nitrate trihydrate as catalyst. All synthesized
compounds were evaluated for their in vitro β-glucuronidase inhibitory activity. In addition,
molecular docking studies were also performed by using MOE docking tools.
Results: Eighteen compounds showed inhibitory activity better than the standard D-saccharic acid
1,4-lactone, a well known β-glucuronidase inhibitor (IC50 = 45.75 ± 2.16 µM). Compound 20 (IC50
= 1.36 ± 0.03 µM) showed an excellent inhibitory activity, thirty-five folds superior to the standard.
Docking results highlighted the role of various chemical moieties at different positions on 2-
oxo-1,2,3,4-tetrahydropyrimidine skeleton in enzyme inhibitory activity.
Conclusion: This study has identified a class of potent β-glucuronidase inhibitors with the potential
to be investigated further.