Design and synthesis of new polyamine quinoline antibiotic enhancers to fight resistant gram-negative P. aeruginosa bacteria

Abstract

The lack of novel drugs in development and the combination of increased incidence of drug-resistant strains of bacteria has created the need for the search for new antimicrobials as well as new original strategies to fight bacterial resistance. In this context, a series of polyamine quinoline derivatives were prepared and biologically evaluated, identifying compounds able to sensitize doxycycline activity towards the Gram-negative bacteria P. aeruginosa. Of note was the identification of antibiotic enhancing analogues whose cytotoxicity ranged from negligible to significant. The mechanism of action of two of the best compounds was studied against P. aeruginosa and S. aureus establishing a different behaviour towards integrity or depolarization of bacterial membranes depending on the structure of the considered polyamine quinoline derivatives.

Keywords

• Antibiotic enhancers
• Antimicrobial agents
• Polyamine quinoline derivatives
• Gram-negative bacteria