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

[Display omitted] • New benzylimidazole QACs with long alkyl chains were synthesized and investigated. • The BnI-14 derivative showed the most promising antimicrobial potential. • The mode of action investigation indicate that BnI-14 induces membrane damage. • BnI-14 binds to DNA suggesting that membrane might not be the only target of QACs. • The low toxicity toward human cells identifies BnI-14 as new potential QACs. 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 N -benzylimidazolium-based QACs may be promising new antimicrobial agents. [ABSTRACT FROM AUTHOR]