Highly Active Small Aminated Quinolinequinones against Drug-Resistant Staphylococcus aureus and Candida albicans

Two subseries of aminated quinolinequinones (AQQs, AQQ1-16) containing electron-withdrawing group (EWG) or electron-donating group (EDG) in aryl amine moiety were successfully synthesized. Antimicrobial activity assessment indicates that some of the AQQs (AQQ8-10 and AQQ12-14) with an EDG in aryl amine exhibited strong antibacterial activity against Gram-positive bacterial strains, including Staphylococcus aureus (ATCC (R) 29213) and Enterococcus faecalis (ATCC (R) 29212). In contrast, AQQ4 with an EWG in aryl amine displayed excellent antifungal activity against fungi Candida albicans (ATCC (R) 10231) with a MIC value of 1.22 mu g/mL. To explore the mode of action, the selected AQQs (AQQ4 and AQQ9) were further evaluated in vitro to determine their antimicrobial activity against each of 20 clinically obtained resistant strains of Gram-positive bacteria by performing antibiofilm activity assay and time-kill curve assay. In addition, in silico studies were carried out to determine the possible mechanism of action observed in vitro. The data obtained from these experiments suggests that these molecules could be used to target pathogens in different modes of growth, such as planktonic and biofilm.

Automated summary

Two subseries of aminated quinolinequinones (AQQs) were successfully synthesized, with electron-withdrawing group or electron-donating group in aryl amine moiety. The AQQs with an electron-donating group exhibited strong antibacterial activity against Gram-positive bacterial strains, while the AQQ with an electron-withdrawing group displayed excellent antifungal activity against Candida albicans. In vitro and in silico studies were conducted to explore the mode of action of the selected AQQs.