3-Arylpropionylhydroxamic acid derivatives as Helicobacter pylori urease inhibitors: Synthesis, molecular docking and biological evaluation
3-Arylpropionylhydroxamic acid derivatives as Helicobacter pylori urease inhibitors: Synthesis, molecular docking and biological evaluation
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3-芳基丙酰异羟肟酸衍生物作为幽门螺杆菌脲酶抑制剂：合成、分子对接和生物学评价
DOI：
10.1016/j.bmc.2016.07.052
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发表时间：
2016-10-01
影响因子：
3.5
通讯作者：
Zhu, Hai-Liang
中科院分区：
文献类型：
--
作者：
Shi, Wei-Kang;Deng, Rui-Cheng;Zhu, Hai-Liang
幽门螺杆菌尿素酶参与多种生理反应，如胃和十二指肠溃疡、腺癌和胃淋巴瘤。因此，抑制脲酶是一个很好的机会来治疗H。由于幽门螺杆菌引起的感染，因此我们集中精力寻找新的脲酶抑制剂。在这里，一系列的芳基丙酰异羟肟酸的合成和评价脲酶抑制。在这些化合物中，3-（2-苄氧基-5-氯苯基）-3-羟基丙酰基异羟肟酸（d24）是最具活性的抑制剂，IC 50为0.15 +/- 0.05 μ M，显示出竞争性和非竞争性方面的混合抑制。动力学数据的非线性拟合给出K-i和K-i '的动力学参数分别为0.13和0.12 μ g·mL（-1）。血浆蛋白结合试验表明，d24表现出中度结合人和兔血浆蛋白。(C)2016爱思唯尔有限公司版权所有。
Helicobacter pylori urease is involved in several physiologic responses such as stomach and duodenal ulcers, adenocarcinomas and stomach lymphomas. Thus, inhibition of urease is taken for a good chance to treat H. pylori-caused infections, we have therefore focused our efforts on seeking novel urease inhibitors. Here, a series of arylpropionylhydroxamic acids were synthesized and evaluated for urease inhibition. Out of these compounds, 3-(2-benzyloxy-5-chlorophenyl)-3-hydroxypropionylhydroxamic acid (d24) was the most active inhibitor with IC50 of 0.15 +/- 0.05 mu M, showing a mixed inhibition with both competitive and uncompetitive aspects. Non-linear fitting of kinetic data gives kinetics parameters of 0.13 and 0.12 mu g.mL(-1) for K-i and K-i', respectively. The plasma protein binding assays suggested that d24 exhibited moderate binding to human and rabbit plasma proteins. (C) 2016 Elsevier Ltd. All rights reserved.