Antibacterial quaternary ammonium agents: Chemical diversity and biological mechanism

Eur J Med Chem. 2022 Dec 5:243:114765. doi: 10.1016/j.ejmech.2022.114765. Epub 2022 Sep 13.

Abstract

Bacterial infections have seriously threatened public health especially with the increasing resistance and the cliff-like decline of the number of newly approved antibacterial agents. Quaternary ammonium compounds (QACs) possess potent medicinal properties with 95 successfully marketed drugs, which also have a long history as antibacterial agents. In this review, we summarize the chemical diversity of antibacterial QACs, divided into chain-like and aromatic ring, reported over the past decade (2012 to mid-2022). Additionally, the structure-activity relationships, mainly covering hydrophobicity, charges and skeleton features, are discussed. In the cases where sufficient information is available, antibacterial mechanisms including biofilm, cell membrane, and intracellular targets are presented. It is hoped that this review will provide sufficient information for medicinal chemists to discover the new generation of antibacterial agents based on QACs.

Keywords: Antibacterial; Mechanism; Quaternary ammonium compounds; Structure-activity relationships.

Publication types

  • Review

MeSH terms

  • Ammonium Compounds*
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Biofilms
  • Microbial Sensitivity Tests
  • Quaternary Ammonium Compounds / chemistry
  • Quaternary Ammonium Compounds / pharmacology

Substances

  • Anti-Bacterial Agents
  • Ammonium Compounds
  • Quaternary Ammonium Compounds