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

2016; Elsevier BV; Volume: 24; Issue: 19 Linguagem: Inglês

10.1016/j.bmc.2016.07.052

1464-3391

Wei-Kang Shi, Rui-Cheng Deng, Pengfei Wang, Qin-Qin Yue, Qi Liu, Kun-Ling Ding, Mei‐Hui Yang, Hongyu Zhang, Si-Hua Gong, Min Deng, Wen-Run Liu, Qiu-Ju Feng, Zhu‐Ping Xiao, Hai‐Liang Zhu,

Biochemical and Molecular Research

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.