title: In vitro activity of a novel antimicrobial agent, TG44, for treatment of Helicobacter pylori infection.
abstract: Due to concerns about the current therapeutic modalities for Helicobacter pylori infection, e.g., the increased emergence of drug-resistant strains and the adverse reactions of drugs currently administered, there is a need to develop an anti-H. pylori agent with higher efficacy and less toxicity. The antibacterial activity of TG44, an anti-H. pylori agent with a novel structural formula, against 54 clinical isolates of H. pylori was examined and compared with those of amoxicillin (AMX), clarithromycin (CLR), and metronidazole (MNZ). Consequently, TG44 inhibited the growth of H. pylori in an MIC range of 0.0625 to 1 microg/ml. The MIC ranges of AMX, CLR, and MNZ were 0.0078 to 8 microg/ml, 0.0156 to 64 microg/ml, and 2 to 128 microg/ml, respectively. The antibacterial activity of TG44 against AMX-, CLR-, and MNZ-resistant strains was nearly comparable to that against drug-susceptible ones. In a pH range of 3 to 7, TG44 at 3.13 to 12.5 microg/ml exhibited potent bactericidal activity against H. pylori in the stationary phase of growth as early as 1 h after treatment began, in contrast to AMX, which showed no bactericidal activity at concentrations of up to 50 microg/ml at the same time point of treatment. TG44 at 25 microg/ml exhibited no antibacterial activity against 13 strains of aerobic bacteria, suggesting that its antibacterial activity against H. pylori is potent and highly specific. The present study indicated that TG44 possesses antibacterial activity which manifests quickly and is potentially useful for eradicating not only the antibiotic-susceptible but also the antibiotic-resistant strains of H. pylori by monotherapy.
authors.affiliation: Quality Assurance Division, Nagase ChemteX Corporation, Fukuchiyama, Kyoto 620-0853, Japan. osamu.kamoda@ncx.nagase.co.jp
authors.forename: Osamu
authors.initials: O
authors.lastname: Kamoda
authors.forename: Kinsei
authors.initials: K
authors.lastname: Anzai
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Mizoguchi
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Shiojiri
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yanagi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishino
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kamiya
mesh_terms: D000658:Amoxicillin / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology*; D017291:Clarithromycin / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D006146:Guanidines / Q000494:pharmacology*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000302:isolation & purification / Q000648:ultrastructure; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008795:Metronidazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure
chemical_list: C510407:4-methylbenzyl 4'-(4-(guanidinomethyl)cyclohexylcarbonyloxy)biphenyl-4-carboxylate; D001565:Benzoates; D006146:Guanidines; D008795:Metronidazole; D000658:Amoxicillin; D017291:Clarithromycin