A series of novel conjugates of nalidixic acid with a marine natural product was designed and synthesized. Their antibacterial and antibiofilm activities were evaluated in vitro against Gram-positive (S. aureus ) and Gram-negative (E. coli and P. aeruginosa) bacteria. Most of the compounds exhibited strong antibacterial activity against S. aureus, E. coli, and P. aeruginosa strains, except for the oxacillin-resistant P. aeruginosa. Among them, compound 2, containing a decyl ammonium fragment, showed the highest antibacterial activity, with MIC values ranging from 2 to 8 μg/mL, superior to those of nalidixic acid. In addition, compound 2 inhibited biofilm formation by standard strains of S. aureus, E. coli, and P. aeruginosa, and by colistin-resistant E. coli by 98-100% at a concentration of 4 μg/mL.

Continuing the search for new antimicrobial agents with antibiofilm activity, bis-quaternary ammonium compounds based on natural (3,5-dibromo-4-hydroxyphenyl)acetic acid derivatives were synthesized. Antibacterial and antibiofilm activity of ammonium salts was evaluated in vitro against S. aureus, E. coli, and P. aeruginosa, including antibiotic-resistant strains. Bis-quaternary ammonium salts 1, 5, and 6 showed antibacterial activity with MIC values ranging from 25.0 to 200.0 μg/mL. Notably, these compounds demonstrated a high level of antibiofilm activity. Ammonium salts 1 and 6 reduced biofilm formation against S. aureus ATCC 25923, P. aeruginosa PA01, E. coli ATCC 25922, and antibiotic-resistant P. aeruginosa by 92 - 97% at a concentration of 100.0 μg/mL. In addition, compounds 1 and 6 inhibited the biofilm formation of antibiotic-resistant E. coli isolate by 60% and 63%, respectively.