title: 3-Arylpropionylhydroxamic acid derivatives as Helicobacter pylori urease inhibitors: Synthesis, molecular docking and biological evaluation.
abstract: 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.
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Wei-Kang
authors: WK
authors: Shi
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Rui-Cheng
authors: RC
authors: Deng
authors: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors: Peng-Fei
authors: PF
authors: Wang
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Qin-Qin
authors: QQ
authors: Yue
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Qi
authors: Q
authors: Liu
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Kun-Ling
authors: KL
authors: Ding
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Mei-Hui
authors: MH
authors: Yang
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Hong-Yu
authors: HY
authors: Zhang
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Si-Hua
authors: SH
authors: Gong
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Min
authors: M
authors: Deng
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Wen-Run
authors: WR
authors: Liu
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Qiu-Ju
authors: QJ
authors: Feng
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China. Electronic address: xiaozhuping2005@163.com.
authors: Zhu-Ping
authors: ZP
authors: Xiao
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China. Electronic address: zhuhl@nju.edu.cn.
authors: Hai-Liang
authors: HL
authors: Zhu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001798:Blood Proteins / Q000378:metabolism; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D062105:Molecular Docking Simulation; D011817:Rabbits; D013329:Structure-Activity Relationship; D014510:Urease / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001798:Blood Proteins; D006877:Hydroxamic Acids; D014510:Urease
keywords: 3-Arylpropionylhydroxamic acid; H. pylori urease inhibitor; Kinetics study; Non-linear fitting; Plasma protein binding