An Investigation into Rigidity-Activity Relationships in BisQAC Amphiphilic Antiseptics

ChemMedChem. 2019 Jan 8;14(1):83-87. doi: 10.1002/cmdc.201800622. Epub 2018 Dec 18.

Abstract

Twenty-one mono- and biscationic quaternary ammonium amphiphiles (monoQACs and bisQACs) were rapidly prepared in order to investigate the effects of rigidity of a diamine core structure on antiseptic activity. As anticipated, the bioactivity against a panel of six bacteria including methicillin-resistant Staphylococcus aureus (MRSA) strains was strong for bisQAC structures, and is clearly correlated with the length of non-polar side chains. Modest advantages were noted for amide-containing side chains, as compared with straight-chained alkyl substituents. Surprisingly, antiseptics with more rigidly disposed side chains, such as those in DABCO-12,12, showed the highest level of antimicrobial activity, with single-digit MIC values or better against the entire bacterial panel, including sub-micromolar activity against an MRSA strain.

Keywords: antiseptics; benzalkonium chloride; bisQAC; methicillin-resistant Staphylococcus aureus (MRSA); quaternary ammonium compounds.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents, Local / chemical synthesis
  • Anti-Infective Agents, Local / chemistry
  • Anti-Infective Agents, Local / pharmacology*
  • Dose-Response Relationship, Drug
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Quaternary Ammonium Compounds / chemical synthesis
  • Quaternary Ammonium Compounds / chemistry
  • Quaternary Ammonium Compounds / pharmacology*
  • Structure-Activity Relationship
  • Surface-Active Agents / chemical synthesis
  • Surface-Active Agents / chemistry
  • Surface-Active Agents / pharmacology*

Substances

  • Anti-Infective Agents, Local
  • Quaternary Ammonium Compounds
  • Surface-Active Agents