title: In vitro and in vivo antibacterial activities of TAK-083, an agent for treatment of Helicobacter pylori infection.
abstract: The antibacterial activity of TAK-083 was tested against 54 clinical isolates of Helicobacter pylori and was compared with those of amoxicillin, clarithromycin, and metronidazole. The growth-inhibitory activity of TAK-083 was more potent than that of amoxicillin, clarithromycin, or metronidazole (the MICs at which 90% of the strains are inhibited were 0.031, 0.125, 64, and 8 microg/ml, respectively). The antibacterial activity of TAK-083 was highly selective against H. pylori; there was a >30-fold difference between the concentration of TAK-083 required to inhibit the growth of H. pylori and that required to inhibit the growth of common aerobic and anaerobic bacteria. Exposure of H. pylori strains to TAK-083 at the MIC or at a greater concentration resulted in an extensive loss of viability. When four H. pylori strains were successively subcultured in the medium containing subinhibitory concentrations of TAK-083, no significant change in the MICs of this compound was observed. TAK-083 strongly inhibited the formation of tryptophanyl-tRNA in H. pylori while exhibiting little effect on the same system in eukaryotes. TAK-083 was efficacious in the treatment of gastric infection caused by H. pylori in Mongolian gerbils. The results presented here indicate that TAK-083 is a promising candidate for the treatment of H. pylori infection.
authors.affiliation: Pharmaceutical Discovery Research Laboratories IV, Pharmaceutical Discovery Research Division, Takeda Chemical Industries, Ltd., Osaka 532-8686, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kanamaru
authors.forename: Y
authors.initials: Y
authors.lastname: Nakano
authors.forename: Y
authors.initials: Y
authors.lastname: Toyoda
authors.forename: K I
authors.initials: KI
authors.lastname: Miyagawa
authors.forename: M
authors.initials: M
authors.lastname: Tada
authors.forename: T
authors.initials: T
authors.lastname: Kaisho
authors.forename: M
authors.initials: M
authors.lastname: Nakao
mesh_terms: D000658:Amoxicillin / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017291:Clarithromycin / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004352:Drug Resistance, Microbial; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008826:Microbial Sensitivity Tests; D010406:Penicillins / Q000494:pharmacology / Q000627:therapeutic use; D013272:Stomach Diseases / Q000188:drug therapy* / Q000382:microbiology; D014369:Tryptophan-tRNA Ligase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D007211:Indoles; D010406:Penicillins; C435764:TAK083; D000658:Amoxicillin; D014369:Tryptophan-tRNA Ligase; D017291:Clarithromycin