The mode of antibacterial action of quaternary N-benzylimidazole salts against emerging opportunistic pathogens

Quaternary ammonium compounds (QACs) are antimicrobial agents displaying a broad spectrum of activity due to their mechanism of action targeting the bacterial membrane. The emergence of bacterial resistance to QACs, especially in times of pandemics, requires the continuous search for new and potent QACs structures. Here we report the synthesis and biological evaluation of QACs based on imidazole derivative, N-benzylimidazole. The antimicrobial activity was tested against a range of pathogenic bacteria and fungi, both ATCC and clinical isolates, showing varying activities ranging in minimal inhibitory concentrations (MICs) from as low as 7 ng/mL. The most promising compound, N-tetradecyl derivative (BnI-14), proved to be very potent against bacterial biofilms, even at sub-MIC doses, suggesting interference with the bacterial growth and/or division process. The BnI-14 treatment induces bacterial membrane disruption, as observed by fluorescence spectroscopy and atomic force microscopy and it also binds to DNA indicating that bacterial membrane might not be the only cellular target of QACs. Most importantly, BnI-14 exhibits low toxicity to healthy human cell lines, suggesting that Nbenzylimidazolium-based QACs may be promising new antimicrobial agents.

Automated summary

Quaternary ammonium compounds (QACs) are antimicrobial agents with broad spectrum activity targeting bacterial membrane. In this study, QACs based on imidazole derivative N-benzylimidazole showed potent antimicrobial activity against pathogenic bacteria, especially against bacterial biofilms. The most promising compound, N-tetradecyl derivative (BnI-14), demonstrated low toxicity to healthy human cells, suggesting potential as a new antimicrobial agent.