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 language | English |
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Article number | 104069 |
Journal | Bioorganic Chemistry |
Volume | 102 |
DOIs | |
State | Published - Sep 2020 |
Bibliographical note
Publisher Copyright:© 2020 Elsevier Inc.
Keywords
- Antimalarial
- Cyclopropenium
- Quaternary ammonium