Minimalistic bis-triarylpyridinium cations: effective antimicrobials against bacterial and fungal pathogens

Abstract

A series of twelve compounds from the family of 2,4,6-triarylpyridinium cations have been synthesized, chemically characterized (¹H, ¹³C NMR, HRMS), and microbiologically evaluated (MIC determination against S. aureus, E. faecalis, E. coli, P. aeruginosa, and C. albicans). These compounds are quaternary ammonium cations (QACs), classified as either mono-QACs or bis-QACs. The mono-QACs are further divided into those with short (three-carbon) and long (twelve-carbon) pendant chains. An additional structural variable is the number of bromine atoms attached to the aromatic rings, ranging from zero to three. The major findings of this study are: (a) bis-QACs exhibit notably higher antimicrobial activity than mono-QACs; (b) an increased number of bromine atoms on the structure appears to diminish antimicrobial properties and (c) one of the compounds (1a) shows particularly promising properties as a broad spectrum antimicrobial, given its low MICs across all five pathogenic microorganisms studied. Preliminary assays with C. albicans show that 1a has a strong mitochondrial activity, causing a remarkable mitochondrial membrane depolarization in this organelle. Taken together, this study positions triarylpyridinium cations—previously unexplored as antimicrobials—as promising candidates for future drug development, especially in light of the growing concern over drug-resistant microorganisms.