The urease enzyme, a metalloenzyme having Ni 2+ ions, is recognized in some bacteria, fungi, and plants. Particularly, it is vital to the progress of infections induced by pathogenic microbes, such as Proteus mirabilis and Helicobacter pylori. Herein, we reported the synthesis of a series of tetrahydropyrimidine derivatives and evaluated their antiurease activity. Finally, quantitative and qualitative analyses of the derivatives were performed via in silico studies. Urease inhibitory activity was determined as the reaction of H. pylori urease with different concentrations of compounds, and thiourea was used as a standard compound. Docking and dynamics methodologies were applied to study the interactions of the best compounds with the amino acids in the active site. All compounds showed good to excellent antiurease activity. The potent compounds were not cytotoxic against the HUVEC normal cell line. Based on the docking study, compound 4e with the highest urease inhibitory activity (IC 50 = 6.81 ± 1.42 µM) showed chelates with both Ni 2+ ions of the urease active site. Further, compound 4f displayed a very good inhibitory activity (IC 50 = 8.45 ± 1.64 μM) in comparison to thiourea (IC 50 = 22.03 ± 1.24 μM). The molecular docking and dynamics simulation results were correlated with the in vitro assay results. Moreover, the derivatives 4a-n followed Lipinski's rule-of-five and had drug-likeness properties.
New series of triazole-tetrahydropyrimidinone(thione) hybrids (9a -g) were synthesized. FT-IR, 1 H-NMR, 13 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-5carboxylate (9c) exhibited the highest urease inhibitory activity (IC 50 = 25.02 μM) among the compounds which was almost similar to thiourea as standard (IC 50 = 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 2 + 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.
Sclareol is a labdane-type phytochemical compound that, due to its pharmacological attributes and historical use in herbal medicine, has attracted noteworthy attention. Numbers of research, mainly through testing on human and animal models, have demonstrated a wide range of effects, by which using sclareol may be considered as an important method in cancer prevention. By using the key words sclareol, cancer, neoplasia, we extracted the articles published up to September 2020 through search in PubMed, SID, ISI Web of Science, Scholar, and Scopus. This study aimed to summarize the research and studies on sclareol and its effects on cancer prevention and treatment.
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