3-Arylpropionylhydroxamic acid derivatives as Helicobacter pylori urease inhibitors: Synthesis, molecular docking and biological evaluation

Publication date: 1 October 2016
Source:Bioorganic & Medicinal Chemistry, Volume 24, Issue 19
Author(s): Wei-Kang Shi, Rui-Cheng Deng, Peng-Fei Wang, Qin-Qin Yue, Qi Liu, Kun-Ling Ding, Mei-Hui Yang, Hong-Yu Zhang, Si-Hua Gong, Min Deng, Wen-Run Liu, Qiu-Ju Feng, Zhu-Ping Xiao, Hai-Liang Zhu
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±0.05μM, showing a mixed inhibition with both competitive and uncompetitive aspects. Non-linear fitting of kinetic data gives kinetics parameters of 0.13 and 0.12μg·mL⁻¹ for Ki and Ki′, respectively. The plasma protein binding assays suggested that d24 exhibited moderate binding to human and rabbit plasma proteins.

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