2-Oxo-1,2,3,4-tetrahydropyrimidines Ethyl Esters as Potent β- Glucuronidase Inhibitors: One-pot Synthesis, In vitro and In silico Studies

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