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Updated: Mar 8, 2026

Preparation of Binary and Ternary Deep Eutectic Systems
Published on: October 31, 2019
Unraveling the cytotoxicity and metabolic pathways of binary natural deep eutectic solvent systems
Yves Paul Mbous1,2, Maan Hayyan1,3, Won Fen Wong4
1University of Malaya Centre for Ionic Liquids (UMCiL), University of Malaya, Kuala Lumpur 50603, Malaysia.
Abstract:
In this study, the anticancer potential and cytotoxicity of natural deep eutectic solvents (NADESs) were assessed using HelaS3, PC3, A375, AGS, MCF-7, and WRL-68 hepatic cell lines. NADESs were prepared from choline chloride, fructose, or glucose and compared with an N,N-diethyl ethanolammonium chloride:triethylene glycol DES. The NADESs (98 ≤ EC50 ≥ 516 mM) were less toxic than the DES (34 ≤ EC50 ≥ 120 mM). The EC50 values of the NADESs were significantly higher than those of the aqueous solutions of their individual components but were similar to those of the aqueous solutions of combinations of their chief elements. Due to the uniqueness of these results, the possibility that NADESs could be synthesized intracellularly to counterbalance the cytotoxicity of their excess principal constituents must be entertained. However, further research is needed to explore this avenue. NADESs exerted cytotoxicity by increasing membrane porosity and redox stress. In vivo, they were more destructive than the DES and induced liver failure. The potential of these mixtures was evidenced by their anticancer activity and intracellular processing. This infers that they can serve as tools for increasing our understanding of cell physiology and metabolism. It is likely that we only have begun to comprehend the nature of NADESs.
Insights
Natural deep eutectic solvents (NADESs) show anticancer potential with lower toxicity than conventional deep eutectic solvents (DESs). NADESs induce cytotoxicity via membrane changes and redox stress, offering insights into cell physiology.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Natural deep eutectic solvents (NADESs) are gaining attention for their potential biological applications.
- Understanding the cytotoxicity and anticancer properties of NADESs is crucial for their therapeutic development.
Purpose of the Study:
- To evaluate the anticancer potential and cytotoxicity of NADESs derived from choline chloride, fructose, or glucose.
- To compare the effects of NADESs with a conventional deep eutectic solvent (DES).
Main Methods:
- Assessed cytotoxicity using HelaS3, PC3, A375, AGS, MCF-7, and WRL-68 cell lines.
- Prepared NADESs from choline chloride and sugars, and a DES from choline chloride and triethylene glycol.
- Determined EC50 values for NADESs and DES, and compared them with aqueous solutions of individual components.
Main Results:
- NADESs exhibited lower toxicity (EC50: 98–516 mM) compared to DES (EC50: 34–120 mM).
- NADESs induced cytotoxicity by increasing membrane porosity and redox stress.
- In vivo studies indicated NADESs were more destructive than DES, causing liver failure.
Conclusions:
- NADESs demonstrate anticancer activity and unique intracellular processing, suggesting potential as tools for studying cell physiology.
- Further research is needed to explore the intracellular synthesis of NADESs and their role in counterbalancing constituent cytotoxicity.
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