ABSTRACT
The 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.
Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Escherichia coli/drug effects , Naphthyridines/pharmacology , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Sulfonamides/pharmacology , Drug Synergism , Fluoroquinolones/pharmacology , Microbial Sensitivity Tests , Norfloxacin/pharmacology , Ofloxacin/pharmacology , Structure-Activity Relationship , BenzenesulfonamidesABSTRACT
This study aimed to evaluate the intrinsic antibacterial activity and antibiotic-enhancing effect of an arylamino methylene derivative (MAD) in association with fluoroquinolones. The antibacterial activity against multiresistant Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli was analyzed by determining the minimum inhibitory concentration (MIC) using the broth micro dilution method. A reduction in the MIC of the fluoroquinolones against strains treated simultaneously with the MAD was interpreted as an enhanced antibiotic activity. While the MAD exhibited no clinically effective action (MIC ≥ 1.024 µg/mL), it was found to significantly potentiate the activity of norfloxacin, ofloxacin and lomefloxacin against all the strains, which may be related to structural similarities between the MAD and quinolones. Our findings suggest that Meldrum's acid arylamino derivatives may represent promising molecules in the elaboration of new drugs to reverse resistance to fluoroquinolones.
ABSTRACT
Two 1,8-naphthyridines were synthesized and found to be fluorescent in solution. These compounds were studied in the presence of Cu(+) and Cu(2+) ions and it was verified that the metal causes the quenching of their fluorescence emission, due to the formation of complexes between the naphthyridine and the metal. A displacement assay was carried out in a DMSO-water mixture with the addition of various anions to the solutions of the complexes, and it was observed that these systems have a high capacity to selectively detect cyanide.
Subject(s)
Chemistry Techniques, Analytical/instrumentation , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Naphthyridines/chemistry , Naphthyridines/chemical synthesis , Chemistry Techniques, Synthetic , Copper/chemistry , Cyanides/analysis , Cyanides/chemistry , Dimethyl Sulfoxide/chemistry , Water/chemistryABSTRACT
The title compound, C11H2Cl5N3O, crystallizes in the monoclinic system with two molecules in the asymmetric unit. The molecules are chemically identical but have different structural parameters. In the three-dimensional packing, the molecules are arranged in dimers that are connected by slipped pi-pi stacking, and these dimers are connected to one another through several C-H...O and Cl...Cl interactions.
