Synthesis and Antimicrobial Activity of Novel 4-Hydroxy-2-quinolone Analogs.

Alkyl quinolone has been proven to be a privileged scaffold in the antimicrobial drug discovery pipeline. In this study, a series of new 4-hydroxy-2-quinolinone analogs containing a long alkyl side chain at C-3 and a broad range of substituents on the C-6 and C-7 positions were synthesized. The antibacterial and antifungal activities of these analogs againstStaphylococcus aureus,Escherichia coli, andAspergillus flavuswere investigated. The structure-activity relationship study revealed that the length of the alkyl chain, as well as the type of substituent, has a dramatic impact on the antimicrobial activities. Particularly, the brominated analogs3jwith a nonyl side chain exhibited exceptional antifungal activities againstA. flavus(half maximal inhibitory concentration (IC50) = 1.05 mu g/mL), which surpassed that of the amphotericin B used as a positive control. The antibacterial activity againstS. aureus, although not as potent, showed a similar trend to the antifungal activity. The data suggest that the 4-hydroxy-2-quinolone is a promising framework for the further development of new antimicrobial agents, especially for antifungal treatment.