Rapid tools to gain insights into the interaction dynamics of new 8 ‐hydroxyquinolines with few fungal lines

Six novel 8 ‐hydroxyquinoline derivatives were synthesized and evaluated. In addition, this work has used tools to better evaluate the interaction of the most active derivatives with fungal cells. Compounds5a and5b showed interesting antimicrobial activity. The EC50 values obtained by combination of time ‐kill studies with mathematical model were similar to the minimal inhibitory concentration, which clarify the potential of these compounds.5a and5b are highly effective, nonirritant molecules and do not exhibit topical toxicity. AbstractThe combination of tools such as time ‐kill assay with subsequent application of mathematical modeling can clarify the potential of new antimicrobial compounds, since minimal inhibitory concentration (MIC) value does not provide a very detailed characterization of antimicrobial activity. Recently, our group has reported that the 8‐h ydroxy‐5‐quinolinesulfonic acid presents relevant antifungal activity. However, its intrinsic acidity could lead to an ionization process, decreasing fungal cell permeability. To overcome this potential problem and enhance activity, the purpose of this study was to synthesize and evaluate a nove l series of hybrids between the 8‐hydroxyquinoline core and sulfonamide and to prove their potential using broth microdilution method, obtaining the pharmacodynamic parameters of the most active derivatives combining time‐kill studies and mathematical modeling and evaluating their toxicity. Comp ound5a was t...
Source: Chemical Biology and Drug Design - Category: Biology Authors: Tags: SPECIAL ISSUE ARTICLE Source Type: research