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.
Tanitame
Akihiko
A
Chemistry Research Laboratories, Dainippon Pharmaceutical Co. Ltd, 33-94 Enoki, Suita, Osaka 564-0053, Japan. akihiko-tanitame@dainippon-pharm.co.jp
Oyamada
Yoshihiro
Y
Ofuji
Keiko
K
Fujimoto
Mika
M
Suzuki
Kenji
K
Ueda
Tomohiko
T
Terauchi
Hideo
H
Kawasaki
Motoji
M
Nagai
Kazuo
K
Wachi
Masaaki
M
Yamagishi
Jun-ichi
J
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