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  • Science & Technology
  • Life Sciences & Biomedicine
  • Chemistry, Medicinal
  • Pharmacology & Pharmacy
  • ammonium compound
  • Antibacterial
  • natural product
  • antiseptic
  • MRSA

Tricepyridinium-inspired QACs yield potent antimicrobials and provide insight into QAC resistance


Journal Title:



Volume 16, Number 3


, Pages 463-466

Type of Work:



Quaternary ammonium compounds (QACs) comprise a large class of surfactants, consumer products, and disinfectants. The recently-isolated QAC natural product tricepyridinium bromide displays potent inhibitory activity against S. aureus but due to its unique structure, its mechanism of action remains unclear. A concise synthetic route to access tricepyridinium analogs was thus designed and four N-alkyl compounds were generated in addition to the natural product. Biological analysis of these compounds revealed that they display remarkable selectivity towards clinically-relevant Gram-positive bacteria exceeding that of commercially-available QACs such as cetylpyridinium chloride (CPC) and benzalkonium chloride (BAC) while having little to no hemolytic activity. Molecular modeling studies revealed that tricepyridinium and shorter-chain N-alkyl analogs may preferentially bind to the QacR transcription factor leading to potential activation of the QAC resistance pathway found in MRSA; however, our newly synthesized analogs are able to overcome this liability.
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