Structural features of piperazinyl-linked ciprofloxacin dimers required for activity against drug-resistant strains of Staphylococcus aureus.
We previously demonstrated that piperazinyl-linked fluoroquinolone dimers possess potent antibacterial activity against drug-resistant strains of Staphylococcus aureus. In this study, we report the preparation and evaluation of a series of incomplete dimers toward ascertaining structural features of piperazinyl-linked ciprofloxacin dimers that render these agents refractory to fluoroquinolone-resistance mechanisms in Staphylococcus aureus.
Kerns
Robert J
RJ
Division of Medicinal and Natural Products Chemistry, The University of Iowa, 52242, Iowa City, IA, USA. robert-kerns@uiowa.edu
Rybak
Michael J
MJ
Kaatz
Glenn W
GW
Vaka
Flamur
F
Cha
Raymond
R
Grucz
Richard G
RG
Diwadkar
Veena U
VU
D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D002939:Ciprofloxacin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000187:drug effects; D024881:Drug Resistance, Bacterial; D009154:Mutation / Q000235:genetics; D010876:Pipemidic Acid / Q000138:chemical synthesis / Q000494:pharmacology; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D010879:Piperazines; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D002939:Ciprofloxacin; D010876:Pipemidic Acid