Phosphonium-ammonium-based di-cationic ionic liquids as antibacterial over the ESKAPE group

Bioorg Med Chem Lett. 2020 Sep 15;30(18):127389. doi: 10.1016/j.bmcl.2020.127389. Epub 2020 Jul 10.

Abstract

Emergence of antibioresistance is currently a major threat of public health worldwide. Hence there is an urge need of finding new antibacterial material. Herein, we report a simple and eco-friendly method to synthesize homo and heterodicationic ionic liquids based on quaternary phosphonium and ammonium salt. In order to investigate the structure activity relationship (SAR) we measured the MICs of a series of 16 derivatives with structural variations (nature of cations and counter-ions, size of linker and alkyl side chains as well as structural symmetry) over a range of Gram-positive and Gram-negative bacterial strains from the ESKAPE group. Some of the tested structures exhibit high antimicrobial activities (MIC = 0.5 mg/L) and are active over a wide range of bacteria from Gram-positive to Gram-negative. Overall, these results reveal the strong potential of di-cationic derivatives as antibacterial agents and the determination of activities from structural features gives decisive information for future synthesis of such di-cationic structures for biocidal purpose.

Keywords: Antimicrobial; Ionic liquids; Phosphonium and ammonium derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkanes / chemistry
  • Ammonium Compounds / chemistry*
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology
  • Cations, Divalent / chemistry
  • Drug Evaluation, Preclinical
  • Humans
  • Ionic Liquids / chemical synthesis*
  • Ionic Liquids / pharmacology
  • Microbial Sensitivity Tests
  • Organophosphorus Compounds / chemistry*
  • Structure-Activity Relationship

Substances

  • Alkanes
  • Ammonium Compounds
  • Anti-Bacterial Agents
  • Cations, Divalent
  • Ionic Liquids
  • Organophosphorus Compounds