title: Bactericidal and morphological effects of NE-2001, a novel synthetic agent directed against Helicobacter pylori.
abstract: The antibacterial activities of NE-2001 were tested against 24 clinical isolates of Helicobacter pylori and compared with those of amoxicillin, clarithromycin, metronidazole, and furazolidone. The MIC(50) and MIC(90) of this synthetic compound on the isolates were 8 and 16 mug/ml, respectively. This action was highly selective against Helicobacter pylori; there was a >4-fold difference between the concentration of NE-2001 required to inhibit the growth of Helicobacter pylori and that required to inhibit the growth of common aerobic and anaerobic bacteria. Exposure of Helicobacter pylori (ATCC43504) to NE-2001 at the MIC (4 mug/ml), or at a greater concentration, resulted in an extensive loss of viability. The phenomenon was also observed at pH levels between 3.0 and 7.0. When two clinical Helicobacter pylori strains were successively cultured at subinhibitory concentrations of NE-2001, no significant changes in the bactericidal effects were found. The morphological alterations of Helicobacter pylori cells (ATCC43504), exposed to NE-2001 at various concentrations for 6 h, were observed using transmission electron microcopy. The bacterium displayed features such as swelling, vacuole-like structures in the cytoplasm, and cell destruction following exposure to NE-2001. The efficacy of NE-2001 was maintained when evaluated in eight clinical isolates resistant to metronidazole and five isolates resistant to both metronidazole and clarithromycin (MIC ranging between 4 and 16 mug/ml). The above-described results suggest that NE-2001 may have the potential to be developed as a candidate agent for the treatment of Helicobacter pylori infection.
authors.affiliation: Department of Biochemistry, Nanjing University, Nanjing 210093, P.R. China.
authors.forename: Guofei
authors.initials: G
authors.lastname: Dai
authors.forename: Ni
authors.initials: N
authors.lastname: Cheng
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Muramatsu
authors.forename: Shudong
authors.initials: S
authors.lastname: Xiao
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Wang
authors.forename: De-Xu
authors.initials: DX
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D017291:Clarithromycin / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D019791:Guanidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development / Q000648:ultrastructure*; D006801:Humans; D008795:Metronidazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D014510:Urease / Q000378:metabolism
chemical_list: C484502:4-(4-methylbenzyl)-4'-(guanidinomethylbenzoyloxy) biphenyl-4-carboxylate hydrochloride; D000900:Anti-Bacterial Agents; D001713:Biphenyl Compounds; D008795:Metronidazole; D014510:Urease; D017291:Clarithromycin; D019791:Guanidine