Synthesis and Antimicrobial Activity of Novel 4-Hydroxy-2-quinolone Analogs
Thitiphong Khamkhenshorngphanuch,
Kittipat Kulkraisri,
Alongkorn Janjamratsaeng,
Napasawan Plabutong,
Arsa Thammahong,
Kanitta Manadee,
Sarisa Na Pombejra,
Tanatorn Khotavivattana
Affiliations
Thitiphong Khamkhenshorngphanuch
Department of General Education, Faculty of Science and Health Technology, Navamindradhiraj University, Bangkok 10300, Thailand
Kittipat Kulkraisri
Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
Alongkorn Janjamratsaeng
Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
Napasawan Plabutong
Antimicrobial Resistance and Stewardship Research Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Arsa Thammahong
Antimicrobial Resistance and Stewardship Research Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Kanitta Manadee
Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
Sarisa Na Pombejra
Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
Tanatorn Khotavivattana
Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
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 against Staphylococcus aureus, Escherichia coli, and Aspergillus flavus were 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 analogs 3j with a nonyl side chain exhibited exceptional antifungal activities against A. flavus (half maximal inhibitory concentration (IC50) = 1.05 µg/mL), which surpassed that of the amphotericin B used as a positive control. The antibacterial activity against S. 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.
