Synthesis and in vitro assessment of the reactivation profile of clinically available oximes on the acetylcholinesterase model inhibited by A‑230 nerve agent surrogate
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F24%3A50021584" target="_blank" >RIV/62690094:18470/24:50021584 - isvavai.cz</a>
Result on the web
<a href="https://link.springer.com/article/10.1007/s00204-024-03821-3" target="_blank" >https://link.springer.com/article/10.1007/s00204-024-03821-3</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00204-024-03821-3" target="_blank" >10.1007/s00204-024-03821-3</a>
Alternative languages
Result language
angličtina
Original language name
Synthesis and in vitro assessment of the reactivation profile of clinically available oximes on the acetylcholinesterase model inhibited by A‑230 nerve agent surrogate
Original language description
The risk of the use of toxic chemicals for unlawful acts has been a matter of concern for different governments and multilateralagencies. The Organisation for the Prohibition of Chemical Weapons (OPCW), which oversees the implementation of theChemical Weapons Convention (CWC), considering recent events employing chemical warfare agents as means of assassination,has recently included in the CWC “Annex on Chemicals” some organophosphorus compounds that are regarded asacting in a similar fashion to the classical G- and V-series of nerve agents, inhibiting the pivotal enzyme acetylcholinesterase.Therefore, knowledge of the activity of the pyridinium oximes, the sole class of clinically available acetylcholinesterasereactivators to date, is plainly justified. In this paper, continuing our research efforts in medicinal chemistry on this class oftoxic chemicals, we synthesized an A-230 nerve agent surrogate and applied a modified Ellman’s assay to evaluate its abilityto inhibit our enzymatic model, acetylcholinesterase from Electrophorus eel, and if the clinically available antidotes areable to rescue the enzyme activity for the purpose of relating the findings to the previously disclosed in silico data for theauthentic nerve agent and other studies with similar A-series surrogates. Our experimental data indicates that pralidoximeis the most efficient compound for reactivating acetylcholinesterase inhibited by A-230 surrogate, which is the opposite ofthe in silico data previously disclosed.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30108 - Toxicology
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Archives of toxicology
ISSN
0340-5761
e-ISSN
1432-0738
Volume of the periodical
98
Issue of the periodical within the volume
10
Country of publishing house
DE - GERMANY
Number of pages
11
Pages from-to
3397-3407
UT code for WoS article
001270948800002
EID of the result in the Scopus database
2-s2.0-85198542353