RESUMO
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.
Assuntos
Antibacterianos/síntese química , Fluoroquinolonas/síntese química , Fluoroquinolonas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Proteínas de Bactérias , Reagentes de Ligações Cruzadas/química , DNA Topoisomerase IV/genética , Dimerização , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Piperazinas/química , Relação Estrutura-AtividadeRESUMO
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.