Squaramide Homoserine Lactone Derivatives and their Abilities to Modulate Pseudomonas aeruginosa Biofilm Formation

Biofilm formation is a bacterial group behavior that is responsible for chronic and persistent infections. In addition, the biofilm mode of growth can decrease the susceptibility of bacteria to antibiotics, leading to antibiotic resistance. The gram-negative opportunistic bacterial pathogen Pseudomonas aeruginosa communicates using autoinducers. One of the key autoinducers is N -acyl- l -homoserine lactones (AHL). Herein, we reported the design and synthesis of squaramide homoserine lactone derivatives and their abilities to inhibit Pseudomonas aeruginosa biofilm formation. Subtle changes in chemical structure resulted in the inversion of biofilm formation activity. Among the AHL mimics tested, the squaramide homoserine lactone with an oligoethylene glycol chain 4H exhibited the most potent anti-biofilm activity, with an IC ₅₀of 0.28 mM. In addition, these AHL derivatives did not affect bacterial survival. Hence, biofilm formation could be suppressed without direct pressure on bacterial growth, preventing the rapid development of bacterial resistance.