A urease inhibitor with good in vivo profile is considered as an alternative agent for treating infections caused by urease-producing bacteria such as Helicobacter pylori. Here, we report a series of N-monosubstituted thioureas, which act as effective urease inhibitors with very low cytotoxicity. One compound (b19) was evaluated in detail and shows promising features for further development as an agent to treat H. pylori caused diseases. Excellent values for the inhibition of b19 against both extracted urease and urease in intact cell were observed, which shows IC50 values of 0.16 ± 0.05 and 3.86 ± 0.10 µM, being 170- and 44-fold more potent than the clinically used drug AHA, respectively. Docking simulations suggested that the monosubstituted thiourea moiety penetrates urea binding site. In addition, b19 is a rapid and reversible urease inhibitor, and displays nM affinity to urease with very slow dissociation (koff=1.60 × 10-3 s-1) from the catalytic domain.

中文翻译：

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N-单芳基乙酰硫脲作为有效的脲酶抑制剂：合成，SAR和生物学评估。

具有良好体内特性的脲酶抑制剂被认为是治疗由产生脲酶的细菌如幽门螺杆菌引起的感染的替代剂。在这里，我们报告了一系列的N-单取代的硫脲，它们作为有效的脲酶抑制剂具有非常低的细胞毒性。对一种化合物（b19）进行了详细评估，并显示出有望作为治疗幽门螺杆菌引起的疾病的试剂进一步开发的特征。观察到b19对完整细胞中提取的脲酶和脲酶均具有优异的抑制作用，其IC50值分别为0.16±0.05和3.86±0.10 µM，分别比临床使用的药物AHA强170倍和44倍。 。对接模拟表明，单取代的硫脲部分穿透尿素结合位点。此外，b19是一种快速且可逆的脲酶抑制剂，