A New Sustainable Approach to Antibiotic Resistance: Development of bis-Quaternary Ammonium Salts From...

The development of highly effective antibiotics and antimicrobials over the centuries has greatly improved human life. However, the irresponsible use of these substances and their release into the environment have led to the emergence of resistant microorganisms. Quaternary ammonium salts (QAS), due to their high efficacy as antibacterial agents and their wide spectrum of activity as disinfectants and antiseptics, represent a possibility to avoid antibiotic resistance. In this work, new bis-cationic QAS, having as common precursor 2,4,6-trichloro-1,3,5-triazine, were synthetized showing high antimicrobial properties (bis-TQAS). The compounds obtained were characterized by ¹H NMR, ¹³C NMR, COSY, HSQC, HMQC, ESI-MS, elemental analysis, and Log P determination. Their antibacterial activity was evaluated against Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, and Listeria monocytogenes. Significant growth inhibition was achieved for all tested strains. Specifically, for the bis-TQAS with C₁₀ alkyl chain, a Log reduction of >5.70 against S. aureus and L. monocytogenes was observed, while the antibacterial Log reduction exceeded 3.60 Log for K. pneumoniae and E. coli strains. In contrast, the performance of the C₁₂ alkyl chain derivative varied; nevertheless, it still demonstrated strong efficacy, with Log reductions exceeding 3.63 for the Gram-positive strains and 4.00 for the Gram-negative strains.