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Novel Phenyl‐Based Bis‐quaternary Ammonium Compounds as Broad‐Spectrum Biocides

Nikita A. Frolov, Ksenia A. Fedoseeva, Karl A. Hansford, A. N. Vereshchagin

2021ChemMedChem17 citationsDOI

Abstract

Herein we report the synthesis and microbiological evaluation of novel phenyl based bis-quaternary ammonium compounds (bis-QACs). Using a simple 2-step synthetic route from dibromo- and dihydroxybenzenes, we obtained a structurally diverse broad panel of bis-QACs with topologically distinct bridging connections between pyridinium heads. Selected analogs possessed potent broad-spectrum biocidal activity against both bacterial and fungal pathogens: methicillin-resistant Staphylococcus aureus (ATCC 43300); Escherichia coli (ATCC 25922), Klebsiella pneumonia (ATCC 700603), Acinetobacter baumannii (ATCC 19606), Pseudomonas aeruginosa (ATCC 27853), Candida albicans (ATCC 90028), Cryptococcus neoformans var. grubii (ATCC 208821). Promising compounds displayed minimum inhibitory concentrations (MIC) values ≤0.25 μg/mL alongside improved cytotoxicity and hemolytic profiles compared to modern antiseptics. Thus, synthesized bis-QACs represent a promising class of biocides with the potential to replace existing household sanitizers.

Topics & Concepts

Acinetobacter baumanniiBiocideCandida albicansMicrobiologyCryptococcus neoformansAntimicrobialStaphylococcus aureusPseudomonas aeruginosaBroad spectrumEscherichia coliKlebsiella pneumoniaeKlebsiella pneumoniaAmmoniumChemistryPyridiniumCytotoxicityBacteriaBiologyCombinatorial chemistryBiochemistryOrganic chemistryIn vitroGeneticsGeneAntimicrobial agents and applicationsEnvironmental Chemistry and AnalysisMolecular Sensors and Ion Detection
Novel Phenyl‐Based Bis‐quaternary Ammonium Compounds as Broad‐Spectrum Biocides | Litcius