Synthesis, Biological Activity Evaluation, Docking and Molecular Dynamics Studies of New Triazole-Tetrahydropyrimidinone(thione) Hybrid Scaffolds as Urease Inhibitors.

New series of triazole-tetrahydropyrimidinone(thione) hybrids (9a-g) were synthesized. FT-IR, H-NMR, C-NMR, elemental analysis and mass spectroscopic studies characterized the structures of the synthesized compounds. Then, the synthesized compounds were screened to determine the urease inhibitory activity. Methyl 4-(4-((1-(2-chlorobenzyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (9c) exhibited the highest urease inhibitory activity (IC =25.02 μM) among the compounds which was almost similar to thiourea as standard (IC =22.32 μM). The docking study of the screened compounds demonstrated that these compounds fit well in the urease active site. Based on the docking study, compound 9c with the highest urease inhibitory activity showed chelates with both Ni ions of the urease active site. Moreover, the molecular dynamic study of the most potent compounds showed that they created important interactions with the active site flap residues, His322, Cys321, and Met317.