1443120-55-5Relevant articles and documents
Re-evolution of the 2-phenylquinolines: Ligand-based design, synthesis, and biological evaluation of a potent new class of staphylococcus aureus NorA efflux pump inhibitors to combat antimicrobial resistance
Sabatini, Stefano,Gosetto, Francesca,Iraci, Nunzio,Barreca, Maria Letizia,Massari, Serena,Sancineto, Luca,Manfroni, Giuseppe,Tabarrini, Oriana,Dimovska, Mirjana,Kaatz, Glenn W.,Cecchetti, Violetta
, p. 4975 - 4989 (2013/07/25)
Overexpression of efflux pumps is an important mechanism by which bacteria evade the effects of antimicrobial agents that are substrates. NorA is a Staphylococcus aureus efflux pump that confers reduced susceptibility to many structurally unrelated agents, including fluoroquinolones, biocides, and dyes, resulting in a multidrug resistant (MDR) phenotype. In this work, a series of 2-phenylquinoline derivatives was designed by means of ligand-based pharmacophore modeling in an attempt to identify improved S. aureus NorA efflux pump inhibitors (EPIs). Most of the 2-phenylquinoline derivatives displayed potent EPI activity against the norA overexpressing strain SA-1199B. The antibacterial activity of ciprofloxacin, when used in combination with some of the synthesized compounds, was completely restored in SA-1199B and SA-K2378, a strain overexpressing norA from a multicopy plasmid. Compounds 3m and 3q also showed potent synergistic activity with the ethidium bromide dye in a strain overexpressing the MepA MDR efflux pump.
