Synthesis and antibacterial activity of novel and potent DNA gyrase inhibitors with azole ring.
The 4-piperidyl moiety and the pyrazole ring in 1-(3-chlorophenyl)-5-(4-phenoxyphenyl)-3-(4-piperidyl)pyrazole 2, which has previously shown improved DNA gyrase inhibition and target-related antibacterial activity, were transformed to other groups and the in vitro antibacterial activity of the synthesized compounds was evaluated. The selected pyrazole, oxazole and imidazole derivatives showed moderate inhibition against DNA gyrase and topoisomerase IV with similar IC(50) values (IC(50)=9.4-25 microg/mL). In addition, many of the pyrazole, oxazole and imidazole derivatives synthesized in this study exhibited potent antibacterial activity against quinolone-resistant clinical isolates and coumarin-resistant laboratory isolates of Gram-positive bacteria with minimal inhibitory concentration values equivalent to those against susceptible strains.
Chemistry Research Laboratories, Dainippon Pharmaceutical Co. Ltd, 33-94 Enoki, Suita, Osaka 564-0053, Japan. akihiko-tanitame@dainippon-pharm.co.jp
Akihiko
A
Tanitame
Yoshihiro
Y
Oyamada
Keiko
K
Ofuji
Mika
M
Fujimoto
Kenji
K
Suzuki
Tomohiko
T
Ueda
Hideo
H
Terauchi
Motoji
M
Kawasaki
Kazuo
K
Nagai
Masaaki
M
Wachi
Jun-ichi
J
Yamagishi
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001393:Azoles / Q000138:chemical synthesis* / Q000494:pharmacology; D027081:DNA Gyrase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D008826:Microbial Sensitivity Tests / Q000706:statistics & numerical data; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology; D059005:Topoisomerase II Inhibitors
D000900:Anti-Bacterial Agents; D001393:Azoles; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D027081:DNA Gyrase