Antibacterial Activity of Bis(4-aminopyridinium) Compounds for Their Potential Use as Disinfectants

The following study presents the initial evaluation (solubility, thermal stability, antibacterial activity, and cytotoxicity) of a series of previously described organic salts, derived from the bis(4-aminopyridinium) cation with different chain lengths, for their potential use as hospital disinfectants. Of the salts studied, those with chain lengths between 2 and 10 carbon atoms (C₂-C₁₀) showed high solubility in water, methanol, and DMSO. All salts exhibited high thermal stability, showing a thermal decomposition temperature (T_5%) above 330 °C. Antibiotic susceptibility testing of the studied <i>E. coli</i>, <i>S. aureus</i>, and <i>S. typhimurium</i> strains confirmed their resistance to different classes of commonly used clinical antibiotics, validating their selection. During the determination of antibacterial activity, the long-chain salts (C₁₀ and C₁₂) showed the greatest activity, with minimum inhibitory concentrations (MICs) from 31.2 μg/mL to 62.5 μg/mL in all the strains studied. Given the high activity of C₁₀ and C₁₂, their cytotoxicity was assessed in HeLa cells. They exhibited no cytotoxic effects after 12 h and only about 5% cytotoxicity after 24 h. Furthermore, the cell viability assay of the most active and water-soluble salt, C₁₀, showed that this salt can interact with the bacterial cytoplasmic membrane, increasing its permeability in both Gram-positive and Gram-negative bacteria. However, these results cannot rule out the possibility that this salt may have more than one site of action within the bacterial cell.