Synthesis of Quinolones and Zwitterionic Quinolonate Derivatives with Broad-Spectrum Antibiotic Activity.

Quinolones are one of the most extensively used therapeutic families of antibiotics. However, the increase in antibiotic-resistant bacteria has rendered many of the available compounds useless. After applying our prediction model of activity against E. coli to a library of 1000 quinolones, two quinolones were selected to be synthesized. Additionally, a series of zwitterionic quinolonates were also synthesized. Quinolones and zwitterionic quinolonates were obtained by coupling the corresponding amine with reagent 1 in acetonitrile. Antibacterial activity was assessed using a microdilution method. All the compounds presented antibacterial activity, especially quinolones 2 and 3, selected by the prediction model, which had broad-spectrum activity. Furthermore, a new type of zwitterionic quinolonate with antibacterial activity was found. These compounds can lead to a new line of antimicrobials, as the structures, and, therefore, their properties, are easily adjustable in the amine in position 4 of the pyridine ring.

New solvent options for in vivo assays in the Galleria mellonella larvae model.

Experimentation in mammals is a long and expensive process in which ethical aspects must be considered, which has led the scientific community to develop alternative models such as that of Galleria mellonella. This model is a cost and time effective option to act as a filter in the drug discovery process. The main limitation of this model is the lack of variety in the solvents used to administer compounds, which limits the compounds that can be studied using this model. Five aqueous (DMSO, MeOH, acetic acid, HCl and NaOH) and four non-aqueous (olive oil, isopropyl myristate, benzyl benzoate and ethyl oleate) solvents was assessed to be used as vehicles for toxicity and antimicrobial activity in vivo assays. All the tested solvents were innocuous at the tested concentrations except for NaOH, which can be used at a maximum concentration of 0.5 M. The toxicity of two additional compounds, 5-aminosalicylic acid and DDT, was also assessed. The results obtained allow for the testing of a broader range of compounds using wax moth larvae. This model appears as an alternative to mammal models, by acting as a filter in the drug development process and reducing costs and time invested in new drugs.