Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, 56189-53141, Ardabil, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, 9138813944, Mashhad, Iran.
Chem Biodivers. 2023 May;20(5):e202300054. doi: 10.1002/cbdv.202300054. Epub 2023 Apr 7.
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.
新系列的三唑-四氢嘧啶酮（硫酮）杂化物（9a-g）被合成。傅里叶变换红外光谱、氢核磁共振、碳核磁共振、元素分析和质谱研究对合成化合物的结构进行了表征。然后，对合成的化合物进行了筛选，以确定其脲酶抑制活性。在这些化合物中，甲基 4-（4-（（1-（2-氯苄基）-1H-1,2,3-三唑-4-基）甲氧基）苯基）-6-甲基-2-硫代-1,2,3,4-四氢嘧啶-5-羧酸酯（9c）表现出最高的脲酶抑制活性（IC=25.02μM），几乎与标准的硫脲相似（IC=22.32μM）。筛选出的化合物的对接研究表明，这些化合物很好地适应了脲酶的活性部位。基于对接研究，具有最高脲酶抑制活性的化合物 9c 与脲酶活性部位的两个 Ni 离子螯合。此外，最有效的化合物的分子动力学研究表明，它们与活性部位瓣状残基 His322、Cys321 和 Met317 产生了重要的相互作用。
