José B. de Araújo-NetoMaria M.C. da SilvaCícera D.de M. Oliveira-TintinoIêda M. BegniniRicardo A. RebeloLuiz E. da SilvaSandro L. MireskiMichele C. NasatoMaria I.L. KrautlerJaime Ribeiro-FilhoAbolghasem SiyadatpanahPolrat WilairatanaHenrique D.M. CoutinhoSaulo R. TintinoFaculty of Tropical Medicine, Mahidol UniversityInfectious Diseases Research Center, Birjand University of Medical SciencesFundacao Oswaldo CruzBirjand University of Medical SciencesUniversidade Regional de BlumenauUniversidade Federal do ParanaUniversidade Regional do Cariri2022-08-042022-08-042021-12-01Molecules. Vol.26, No.23 (2021)142030492-s2.0-85121150091https://repository.li.mahidol.ac.th/handle/123456789/75901The search for new antibacterial agents has become urgent due to the exponential growth of bacterial resistance to antibiotics. Nitrogen-containing heterocycles such as 1,8-naphthyridine derivatives have been shown to have excellent antimicrobial properties. Therefore, the purpose of this study was to evaluate the antibacterial and antibiotic-modulating activities of 1,8-naphthyridine derivatives against multi-resistant bacterial strains. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of the following compounds: 7-acetamido-1,8-naphthyridin-4(1H)-one and 3-trifluoromethyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide. The antibiotic-modulating activity was analyzed using subinhibitory concentrations (MIC/8) of these compounds in combination with norfloxacin, ofloxacin, and lomefloxacin. Multi-resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were used in both tests. Although the compounds had no direct antibacterial activity (MIC ≥ 1.024 µg/mL), they could decrease the MIC of these fluoroquinolones, indicating synergism was obtained from the association of the compounds. These results suggest the existence of a structure–activity relationship in this group of compounds with regard to the modulation of antibiotic activity. Therefore, we conclude that 1,8-naphthyridine derivatives potentiate the activity of fluoroquinolone antibiotics against multi-resistant bacterial strains, and thereby interesting candidates for the development of drugs against bacterial infections caused by multidrug resistant strains.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyChemistryPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.3390/molecules26237400