Oxime K033-Reactivation Activity of Cholinesterases Inhibited by Various Nerve Agents and Organophosphorus Pesticides

Author(s): Kamil Kuca*, Kamil Musilek, Daniel Jun, Jaroslav Pejchal, Ondrej Krejcar, Marek Penhaker, Qinghua Wu, Raquel O. Lopes, Teodorico C. Ramalho, Tanos C.C. Franca, Eugenie Nepovimova, Ondrej Soukup

Journal Name: Letters in Drug Design & Discovery

Volume 15 , Issue 11 , 2018

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Graphical Abstract:


Background: Oxime K033 was considered a promising drug candidate originally developed for the treatment of nerve agent poisoning. This study summarizes its potency to reactivate in vitro acetylcholinesterase inhibited by several nerve agents (tabun, sarin, cyclosarin, soman, VX, Russian VX), mimic agent (DFP) and organophosphorus pesticide (chlorpyrifos) to show whether this compound might be used in cases of nerve agent or pesticide poisoning and considered as a so-called “broad spectrum reactivator”.

Methods: Moreover, docking studies of tested oxime with human AChE (HssAChE) complexed with several OPs were performed in order to verify its stability, binding modes and ability to adopt favourable conformations and to perform the reactivation reaction with each OP under experimental study.

Results & Conclusion: According to the obtained results, K033 could not be considered a universal antidote due to its poor reactivation activity in the case of tabun-, soman- and DFP-inhibited rat acetylcholinesterase. On the contrary, its very good in vitro potency in human-relevant doses for cyclosarin inhibition is highlighted.

Keywords: Oxime, K033, nerve agent, pesticide, antidote, cholinesterase, reactivator.

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Article Details

Year: 2018
Page: [1124 - 1130]
Pages: 7
DOI: 10.2174/1570164615666180713112238
Price: $65

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