Brominated oxime nucleophiles are efficiently reactivating cholinesterases inhibited by nerve agents

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F24%3A50021654" target="_blank" >RIV/62690094:18470/24:50021654 - isvavai.cz</a>
Alternative codes found
RIV/00179906:_____/24:10484025 RIV/60162694:G44__/25:00563523
Result on the web
<a href="https://link.springer.com/article/10.1007/s00204-024-03791-6" target="_blank" >https://link.springer.com/article/10.1007/s00204-024-03791-6</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00204-024-03791-6" target="_blank" >10.1007/s00204-024-03791-6</a>

Result language
angličtina
Original language name
Brominated oxime nucleophiles are efficiently reactivating cholinesterases inhibited by nerve agents
Original language description
Six novel brominated bis-pyridinium oximes were designed and synthesized to increase their nucleophilicity and reactivation ability of phosphorylated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Their pKa was valuably found lower to parent non-halogenated oximes. Stability tests showed that novel brominated oximes were stable in water, but the stability of di-brominated oximes was decreased in buffer solution and their degradation products were prepared and characterized. The reactivation screening of brominated oximes was tested on AChE and BChE inhibited by organophosphorus surrogates. Two mono-brominated oximes reactivated AChE comparably to non-halogenated analogues, which was further confirmed by reactivation kinetics. The acute toxicity of two selected brominated oximes was similar to commercially available oxime reactivators and the most promising brominated oxime was tested in vivo on sarin- and VX-poisoned rats. This brominated oxime showed interesting CNS distribution and significant reactivation effectiveness in blood. The same oxime resulted with the best protective index for VX-poisoned rats.
Czech name
—
Czech description
—

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

Project
<a href="/en/project/GA21-03000S" target="_blank" >GA21-03000S: Modified nucleophiles for reactivation of cholinesterases inhibited by organophosphorus compounds</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Similar results(10)