SAR study to find optimal cholinesterase reactivator against organophosphorous nerve agents and pesticides

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61988987%3A17110%2F16%3AA1801RWQ" target="_blank" >RIV/61988987:17110/16:A1801RWQ - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/16:10330207 RIV/60162694:G44__/16:43875688 RIV/62690094:18470/16:50005166

Výsledek na webu

<a href="http://dx.doi.org/10.1007/s00204-016-1827-3" target="_blank" >http://dx.doi.org/10.1007/s00204-016-1827-3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00204-016-1827-3" target="_blank" >10.1007/s00204-016-1827-3</a>

Jazyk výsledku

angličtina

Název v původním jazyce

SAR study to find optimal cholinesterase reactivator against organophosphorous nerve agents and pesticides

Popis výsledku v původním jazyce

Irreversible inhibition of acetylcholinesterase (AChE) by organophosphates leads to many failures in living organism and ultimately in death. Organophosphorus compounds developed as nerve agents such as tabun, sarin, soman, VX and others belong to the most toxic chemical warfare agents and are one of the biggest threats to the modern civilization. Moreover, misuse of nerve agents together with organophosphorus pesticides (e.g. malathion, paraoxon, chlorpyrifos, etc.) which are annually implicated in millions of intoxications and hundreds of thousand deaths reminds us of insufficient protection against these compounds. Basic treatments for these intoxications are based on immediate administration of atropine and acetylcholinesterase reactivators which are currently represented by mono- or bis-pyridinium aldoximes. However, these antidotes are not sufficient to ensure 100 % treatment efficacy even they are administered immediately after intoxication, and in general, they possess several drawbacks. Herein, we have reviewed new efforts leading to the development of novel reactivators and proposition of new promising strategies to design novel and effective antidotes. Structure-activity relationships and biological activities of recently proposed acetylcholinesterase reactivators are discussed and summarized. Among further modifications of known oximes, the main attention has been paid to dual binding site ligands of AChE as the current mainstream strategy. We have also discussed new chemical entities as potential replacement of oxime functional group.

Název v anglickém jazyce

SAR study to find optimal cholinesterase reactivator against organophosphorous nerve agents and pesticides

Popis výsledku anglicky

Irreversible inhibition of acetylcholinesterase (AChE) by organophosphates leads to many failures in living organism and ultimately in death. Organophosphorus compounds developed as nerve agents such as tabun, sarin, soman, VX and others belong to the most toxic chemical warfare agents and are one of the biggest threats to the modern civilization. Moreover, misuse of nerve agents together with organophosphorus pesticides (e.g. malathion, paraoxon, chlorpyrifos, etc.) which are annually implicated in millions of intoxications and hundreds of thousand deaths reminds us of insufficient protection against these compounds. Basic treatments for these intoxications are based on immediate administration of atropine and acetylcholinesterase reactivators which are currently represented by mono- or bis-pyridinium aldoximes. However, these antidotes are not sufficient to ensure 100 % treatment efficacy even they are administered immediately after intoxication, and in general, they possess several drawbacks. Herein, we have reviewed new efforts leading to the development of novel reactivators and proposition of new promising strategies to design novel and effective antidotes. Structure-activity relationships and biological activities of recently proposed acetylcholinesterase reactivators are discussed and summarized. Among further modifications of known oximes, the main attention has been paid to dual binding site ligands of AChE as the current mainstream strategy. We have also discussed new chemical entities as potential replacement of oxime functional group.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

<a href="/cs/project/GA15-16701S" target="_blank" >GA15-16701S: Koncept nekvarterních reaktivátorů AChE jakožto antidot otrav organofosfáty - nová naděje či slepá cesta?</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

ARCHIVES OF TOXICOLOGY

ISSN

0340-5761

e-ISSN

1432-0738

Svazek periodika

90

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

29

Strana od-do

2831-2859

Kód UT WoS článku

000387697600001

EID výsledku v databázi Scopus

2-s2.0-84984788964