title: Synthesis and evaluation of N-analogs of 1,2-diarylethane as Helicobacter pylori urease inhibitors.
abstract: Therapies based on urease inhibition are now seriously considered as the first line of treatment for infections caused by Helicobacter pylori. However, the present inhibitors are ineffective or unstable in highly acidic gastric juice. Here, we report a series of benzylanilines as effective inhibitors of H. pylori urease. Out of the obtained twenty-one compounds, N-(3,4-dihydroxybenzyl)-4-nitroaniline (4) was evaluated in detail and shows promising features for development as anti-H. pylori agent. Excellent potency against urease in both cell-free extract and intact cell was observed at low concentrations of 4 (IC50=0.62 ± 0.04 and 1.92 ± 0.09 μM), which showed over 29- and 54-fold increase in potency with respect to the positive control AHA. The SAR analysis revealed that protection of 3,4-dihydroxy group of 4 as methoxy or changes of 4-NO2 will result in a moderate to dramatic decrease in potency.
authors.affiliation: 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: xiaozhuping2005@163.com.
authors.forename: Zhu-Ping
authors.initials: ZP
authors.lastname: Xiao
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Wei-Kang
authors.initials: WK
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Wang
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Zeng
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Ji-Rong
authors.initials: JR
authors.lastname: Zhang
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhu
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Miao
authors.initials: M
authors.lastname: Peng
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Peng
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Lin
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China. Electronic address: oyhmail@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Ouyang
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Peng
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Guang-Cheng
authors.initials: GC
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China. Electronic address: zhuhl@nju.edu.cn.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004980:Ethane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D016480:Helicobacter pylori / Q000201:enzymology*; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D014510:Urease / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D014510:Urease; D004980:Ethane
keywords: Benzylaniline; Molecular docking; Peptic ulcer; Urease inhibitor