AimThe goal of this study was to increase knowledge about the antimicrobial activity of some synthetic Riparin-derived compounds, alone or in combination with fluoroquinolone antibiotics, against a strain of Staphylococcus aureus resistant to fluoroquinolone by way of overexpression of the NorA efflux pump. Methods and ResultsMicrodilution tests showed that Riparins A and B did not show any significant antibacterial activity against Staph.aureus strains. On the other hand, the intrinsic antibacterial activity increased with increasing lipophilicity of the compounds, in the following order: Riparin-D (MIC 256gml(-1); Log P 295) < Riparin-C (MIC 102gml(-1); Log P 322) < Riparin-E (MIC 16gml(-1); Log P 357). The addition of all riparins to growth media at subinhibitory concentrations caused an increase in the antibacterial activity of antibiotics against the NorA-overexpressing test strain. Riparin-B, which has two methoxyl groups at the phenethyl moiety, showed the best modulatory effect. ConclusionsRiparin-E is a good anti-staphylococci agent, while Riparin-B functions as a NorA efflux pump inhibitor. Significance and Impact of the StudyOur data suggest the possibility of using Riparin-B in combination with norfloxacin or ciprofloxacin for therapy of infections caused by multi-drug resistant Staph.aureus.