Asymmetric trisalkylamine cyclopropenium derivatives with antimicrobial activity

Chen Belay, Noam Y. Steinman, Luis M. Campos, Ron Dzikowski, Jacob Golenser, Abraham J. Domb*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Cationic molecules are found in abundance as antimicrobial agents with a well-defined mechanism of action and significant therapeutic benefits. Quaternary ammonium-containing compounds are frequently employed due to their facile synthesis and tunable properties. Over time, however, bacterial resistance to these compounds has become a significant obstacle. We report here a series of asymmetric trisalkylamine cyclopropenium cationic derivatives as chemical isosteres of quaternary ammonium compounds, capable of strong antimicrobial activity and overcoming microbial resistance. These small molecules were prepared by one-pot reaction of tetrachlorocyclopropene (TCC) with unhindered secondary amines in the presence of Hünig's base. In this work we describe the synthesis, purification, and characterization of five trisamino-cyclopropenium derivatives and confirm their structures by spectral analysis and mass-spectrometry. Three of the compounds displayed considerable antimalarial activity (IC50 < 0.1 µM) without demonstrating significant toxic effects in vitro (TC50 > 1 µM). This class of cyclopropenium-based compounds provides an opening for the discovery of potent and non-toxic antimicrobial agents.

Original languageAmerican English
Article number104069
JournalBioorganic Chemistry
Volume102
DOIs
StatePublished - Sep 2020

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Inc.

Keywords

  • Antimalarial
  • Cyclopropenium
  • Quaternary ammonium

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