Piperazinyl-linked fluoroquinolone dimers possessing potent antibacterial activity against drug-resistant strains of Staphylococcus aureus.
The synthesis of symmetric and asymmetric piperazinyl-linked dimers of the fluoroquinolone class of antibiotics is described. Specific dimers are shown to possess potent antibacterial activity against drug-resistant strains of Staphylococcus aureus, including strains possessing resistance due to the NorA multidrug efflux pump and a mutation in the quinolone resistance-determining region of topoisomerase IV.
Division of Medicinal and Natural Products Chemistry, The University of Iowa, Iowa City 52242, USA. robert-kerns@uiowa.edu
Robert J
RJ
Kerns
Michael J
MJ
Rybak
Glenn W
GW
Kaatz
Flamur
F
Vaka
Raymond
R
Cha
Richard G
RG
Grucz
Veena U
VU
Diwadkar
Tracey D
TD
Ward
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001426:Bacterial Proteins; D003432:Cross-Linking Reagents / Q000737:chemistry; D027101:DNA Topoisomerase IV / Q000235:genetics; D019281:Dimerization; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000138:chemical synthesis* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010879:Piperazines / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003432:Cross-Linking Reagents; D027101:DNA Topoisomerase IV; D024841:Fluoroquinolones; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010879:Piperazines; C075040:NorA protein, Staphylococcus