Are the current commercially available oximes capable of reactivating acetylcholinesterase inhibited by the nerve agents of the A-series?

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F22%3A50019202" target="_blank" >RIV/62690094:18470/22:50019202 - isvavai.cz</a>

Result on the web

<a href="https://link.springer.com/article/10.1007/s00204-022-03316-z" target="_blank" >https://link.springer.com/article/10.1007/s00204-022-03316-z</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00204-022-03316-z" target="_blank" >10.1007/s00204-022-03316-z</a>

Result language

angličtina

Original language name

Are the current commercially available oximes capable of reactivating acetylcholinesterase inhibited by the nerve agents of the A-series?

Original language description

The misuse of novichok agents in assassination attempts has been reported in the international media since 2018. These relatively new class of neurotoxic agents is claimed to be more toxic than the agents of the G and V series and so far, there is no report yet in literature about potential antidotes against them. To shed some light into this issue, we report here the design and synthesis of NTMGMP, a surrogate of A-242 and also the first surrogate of a novichok agent useful for experimental evaluation of antidotes. Furthermore, the efficiency of the current commercial oximes to reactivate NTMGMP-inhibited acetylcholinesterase (AChE) was evaluated. The Ellman test was used to confirm the complete inhibition of AChE, and to compare the subsequent rates of reactivation in vitro as well as to evaluate aging. In parallel, molecular docking, molecular dynamics and MM-PBSA studies were performed on a computational model of the human AChE (HssAChE)/NTMGMP complex to assess the reactivation performances of the commercial oximes in silico. Experimental and theoretical studies matched the exact hierarchy of efficiency and pointed to trimedoxime as the most promising commercial oxime for reactivation of AChE inhibited by A-242. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30108 - Toxicology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Archives of toxicology

ISSN

0340-5761

e-ISSN

1432-0738

Volume of the periodical

96

Issue of the periodical within the volume

6

Country of publishing house

DE - GERMANY

Number of pages

14

Pages from-to

2559-2572

UT code for WoS article

000806678500001

EID of the result in the Scopus database

2-s2.0-85131436892