Alkyl quinolone has been proven to be a privileged scaffold in the antimicrobial drug\ndiscovery pipeline. In this study, a series of new 4-hydroxy-2-quinolinone analogs containing a long\nalkyl side chain at C-3 and a broad range of substituents on the C-6 and C-7 positions were synthesized.\nThe antibacterial and antifungal activities of these analogs against Staphylococcus aureus, Escherichia coli,\nand Aspergillus flavus were investigated. The structure-activity relationship study revealed that the\nlength of the alkyl chain, as well as the type of substituent, has a dramatic impact on the antimicrobial\nactivities. Particularly, the brominated analogs 3j with a nonyl side chain exhibited exceptional\nantifungal activities against A. flavus (half maximal inhibitory concentration (IC50) = 1.05 microg/mL),\nwhich surpassed that of the amphotericin B used as a positive control. The antibacterial activity\nagainst S. aureus, although not as potent, showed a similar trend to the antifungal activity. The data\nsuggest that the 4-hydroxy-2-quinolone is a promising framework for the further development of\nnew antimicrobial agents, especially for antifungal treatment.
Loading....