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A new article was published in Chemico-Biological Interaction by Sustainable Chemistry and Engineering research group of Tallinn University of Technology, in collaboration with colleagues from Czech Republic, Brazil, and UK. This study sheds light on use of existing competence on designing biodegradable molecules in an innovative way – to develop novel antidotes against organophosphate poisoning.
Acetyl cholinesterase (AChE) is an enzyme involved in the proper functioning of the nervous system. It catalyzes the breakdown of neurotransmitter acetylcholine. Inhibition of human AChE is the main mechanism for toxicity of so-called nerve agents – chemical warfare agents like Sarin, VX, or recently renowned Novichok. This results in the accumulation of acetylcholine at synapses, leading to nervous and respiratory failure and death within minutes. Although the major world powers have agreed to abandon the use of chemical weapons and destroy their pilestocks, the key intermediates are sometimes relatively easy to synthesize and use by the terrorists or rogue states. Despite numerous efforts of researchers, there are still no universal reactivator sufficiently effective against all nerve agents.
Yevgen Karpichev, a PI of the research group, says: “This work is our le mariage parfait between sustainable approach to make new molecular platforms and searching for new antidotes – reactivators of acetylcholinesterase, inhibited by toxic organophosphorus compounds. We have been developing for years the building blocks for biodegradable ionic liquids (IL) and surfactants, using so-called “benign-by-design” approach, to be sustainable in our research. At the same time, we worked on the projects devoted to detoxification of organophosphorus toxicants and knew this chemistry by heart. We know that the principles of sustainability are not always applied to the chemistry “hard times”. In this work, we applied two our competences at once.”
The novel compounds reveal a remarkable activity against the AChE inhibited by nerve agent VX, exceeding conventional reactivators. They are found to be non-toxic to bacteria and fungi, possess low toxicity against mammalian cells, are not persistent, but stable in human plasma.
“This work represents state-of the-art study in this field and will be used for improvement of human acetylcholinesterase reactivators critically important for treatment of organophosphates poisoning” – added the research group leader.
The full article can be found here: https://doi.org/10.1016/j.cbi.2023.110735
This article was originally published on the Tallinn University of Technology webpage.
Additional information: TalTech Department of Chemistry and Biotechnology, Dr. Yevgen Karpichev, yevgen.karpichev@taltech.ee
