title: A 4-aminofurazan derivative-A189-inhibits assembly of bacterial cell division protein FtsZ in vitro and in vivo.
abstract: Out of 95,000 commercially available chemical compounds screened by the anucleate cell blue assay, 138 selected hit compounds were further screened. As a result, A189, a 4-aminofurazan derivative was found to inhibit FtsZ GTPase with an IC(50) of 80 mug/ml and to exhibit antibacterial activity against Staphylococcus aureus and Escherichia coli. Light scattering demonstrated that A189 inhibited FtsZ assembly in vitro, and microscopic observation of A189-treated E. coli indicated that A189 perturbed FtsZ ring formation and made bacterial cells filamentous. However, nucleoids staining with DAPI revealed that A189 did not affect DNA replication and chromosome segregation in bacterial filamentous cells. Furthermore, A189 made sulA-deleted E. coli cells filamentous. Taken together, these findings suggest that A189 inhibits FtsZ GTPase activity, resulting in perturbation of FtsZ ring formation, which leads to bacterial cell death.
authors.affiliation: Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co. Ltd., 2-6-8 Doshomachi, Chuo-ku, Osaka, Osaka 541-0045, Japan. hideaki-ito@ds-pharma.co.jp
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oyamada
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tanitame
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yoshida
authors.forename: Sakuo
authors.initials: S
authors.lastname: Yamada
authors.forename: Masaaki
authors.initials: M
authors.lastname: Wachi
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Yamagishi
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects; D010069:Oxadiazoles / Q000494:pharmacology*
chemical_list: C516147:A 189 compound; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria; D010069:Oxadiazoles