title: Synthesis, molecular docking and biological evaluation of metronidazole derivatives as potent Helicobacter pylori urease inhibitors.
abstract: Fourteen metronidazole derivatives (compounds 3a-f and 4b-h) have been synthesized by coupling of metronidazole and salicylic acid derivatives. All of them are reported for the first time. Their chemical structures are characterized by (1)H NMR, MS, and elemental analysis. The inhibitory activities against Helicobacter pylori urease have been investigated in vitro and many compounds have showed promising potential inhibitory activities of H. pylori urease. The effect of compounds 4b (IC(50)=26 microM) and 4 g (IC(50)=12 microM) was comparable with that of acetohydroxamic acid, a well known H. pylori urease inhibitor used as a positive control. The experimental values of IC(50) showed that inhibitor was potent urease inhibitor. A docking analysis using the autodock 4.0 program could explain the inhibitory activities of compound 4 g against H. pylori urease.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Mao
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: Lv
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Huan-Qiu
authors.initials: HQ
authors.lastname: Li
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D016480:Helicobacter pylori / Q000201:enzymology*; D008795:Metronidazole / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014510:Urease / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C545771:(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl4-methyl-2-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy)benzoate; C545772:(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl5-bromo-2-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy)benzoate; D000890:Anti-Infective Agents; D008795:Metronidazole; D014510:Urease