title: [Inhibitory activity of NM394, the active form of prodrug prulifloxacin against type II topoisomerase from Pseudomonas aeruginosa].
abstract: The inhibitory activity of NM394, the active form of the prodrug prulifloxacin, against type II topoisomerase from Pseudomonas aeruginosa was compared with those of ciprofloxacin (CPFX), levofloxacin (LVFX) and gatifloxacin (GFLX). The 50% inhibitory concentrations (IC50S) of NM394 for supercoiling activity of DNA gyrase and the decatenation activity of topoisomerase IV were 1.21 and 21.1 micrograms/ml, respectively. The IC50 of NM394 was equal to that of CPFX and lower than those of LVFX and GFLX. The inhibitory activity of the four drugs for DNA gyrase was also corresponding to the antimicrobial activity of the drugs for P. aeruginosa PAO1. The IC50S of the drugs tested for the decatenation activity of topoisomerase IV were from 17.4 to 24.2 times higher than those for the supercoiling activities of DNA gyrase. These results show that DNA gyrase is more sensitive to quinolones than is topoisomerase IV and may be a primary target of quinolones in P. aeruginosa. We concluded that NM394 exerts the potent antimicrobial activity through its strong inhibitory activity for DNA gyrase.
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Tani
authors.forename: Kazunori
authors.initials: K
authors.lastname: Maebashi
authors.forename: Minako
authors.initials: M
authors.lastname: Araake
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Watabe
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D027101:DNA Topoisomerase IV / Q000037:antagonists & inhibitors; D004148:Dioxolanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024841:Fluoroquinolones; D000077734:Gatifloxacin; D064704:Levofloxacin; D015242:Ofloxacin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011355:Prodrugs / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D015363:Quinolones / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors
chemical_list: D000890:Anti-Infective Agents; D004148:Dioxolanes; D024841:Fluoroquinolones; D010879:Piperazines; D011355:Prodrugs; D015363:Quinolones; D059005:Topoisomerase II Inhibitors; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin; C074190:ulifloxacin; D027101:DNA Topoisomerase IV; C074191:prulifloxacin; D000077734:Gatifloxacin