Synthesis and Biological Evaluation of Quinoline Derivatives as a Novel Class of Broad-Spectrum Antibacterial Agents

摘要

Nineteen new quinoline derivatives were prepared via the Mannich reaction and evaluated for their antibacterial activities against both Gram-positive (G⁺) and Gram-negative (G⁻) bacteria, taking compound >1 as the lead. Among the target compounds, quinolone coupled hybrid >5d exerted the potential effect against most of the tested G⁺ and G⁻ strains with MIC values of 0.125–8 μg/mL, much better than those of >1. Molecular-docking assay showed that compound >5d might target both bacterial LptA and Top IV proteins, thereby displaying a broad-spectrum antibacterial effect. This hybridization strategy was an efficient way to promote the antibacterial activity of this kind, and compound >5d was selected for the further investigation, with an advantage of a dual-target mechanism of action.