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

TL;DR

This study evaluates new organic salts as potential hospital disinfectants, finding that longer-chain compounds show strong antibacterial activity with low cytotoxicity.

Contribution

The study introduces bis(4-aminopyridinium) salts as novel disinfectant candidates with promising antibacterial and low cytotoxic properties.

Findings

Long-chain salts (C10 and C12) showed the highest antibacterial activity with MICs between 31.2 and 62.5 μg/mL.

C10 and C12 exhibited minimal cytotoxicity in HeLa cells, with only 5% after 24 hours.

C10 increases bacterial membrane permeability in both Gram-positive and Gram-negative bacteria.

Abstract

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 (T5%) above 330 °C. Antibiotic susceptibility testing of the studied E. coli, S. aureus, and S. typhimurium 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.

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