Asymmetric trisalkylamine cyclopropenium derivatives with antimicrobial activity
Chen Belay1, Noam Y Steinman1, Luis M Campos2
1Institute of Drug Research, School of Pharmacy-Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Bioorganic Chemistry
|July 20, 2020
Summary
New cationic cyclopropenium compounds show potent antimicrobial and antimalarial activity, overcoming existing resistance. These novel molecules offer a promising avenue for developing effective and safe antimicrobial agents.
Area of Science:
- Medicinal Chemistry
- Organic Synthesis
- Drug Discovery
Background:
- Cationic molecules, particularly quaternary ammonium compounds, are widely used as antimicrobial agents.
- Bacterial resistance to existing antimicrobial compounds is a growing global health concern.
- There is a need for novel antimicrobial agents with different mechanisms of action to overcome resistance.
Purpose of the Study:
- To synthesize and characterize novel asymmetric trisalkylamine cyclopropenium cationic derivatives.
- To evaluate the antimicrobial and antimalarial activity of these novel compounds.
- To assess the in vitro toxicity of the synthesized compounds.
Main Methods:
- One-pot synthesis of trisamino-cyclopropenium derivatives from tetrachlorocyclopropene and secondary amines.
- Purification and structural confirmation using spectral analysis and mass spectrometry.
- In vitro evaluation of antimalarial activity and cytotoxicity.
Main Results:
- Five trisamino-cyclopropenium derivatives were successfully synthesized and characterized.
- Three compounds exhibited significant antimalarial activity with IC50 values below 0.1 µM.
- These compounds demonstrated low in vitro toxicity with TC50 values above 1 µM.
Conclusions:
- Trisalkylamine cyclopropenium derivatives represent a novel class of potent antimicrobial agents.
- These compounds show promise in overcoming microbial resistance.
- This new class of cyclopropenium-based compounds offers potential for developing non-toxic and effective antimicrobial therapies.
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