Although the wide arsenal of drugs available to treat bacterial infections, emerging drug-resistant bacterial pathogens have recently highlighted an urgent need to find new more effective and less toxic therapeutic agents.Fluoroquinolones are antibiotics showing a concentration-dependent bactericidal capacity due to the activity inhibition of DNA-gyrase and Topoisomerase IV, which are enzymes essential for bacterial DNA replication. Among them, norfloxacin is mainly active on Gram-(+) bacteria. Naphthoquinones are secondary metabolites showing different biological activities, including cytotoxic, antibacterial and antifungal effects. In particular, the efficacy of natural and synthetic 1,4-naphthoquinone derivatives is likely due to their oxidizing /reducing capability, through which they destroy cellular targets as nucleic acids. Hybrid molecules are obtained combining structural features of two or more bioactive compounds, in order to obtain new therapeutic agents able, not only to reduce undesirable side effects of the parent drugs, but also to inhibit more biological targets, hopefully with a better therapeutic property than the administration of combined single-target drugs. With the aim to apply this strategy in the study of new potential antimicrobial agents, we have designed four molecules by docking calculation on S.aureus DNA gyrase (pdb code: 5CDQ). These compounds were synthesized by the reaction of norfloxacin with the corresponding quinones, and their activities evaluated against both bacteria and fungi, in comparison with synthetic precursors.