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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F18%3A50014625" target="_blank" >RIV/62690094:18470/18:50014625 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/18:10380498 RIV/60162694:G44__/18:43889581 RIV/61989100:27240/18:10241741

Výsledek na webu

<a href="http://www.eurekaselect.com/node/163753/article/oxime-k033-reactivation-activity-of-cholinesterases-inhibited-by-various-nerve-agents-and-organophosphorus-pesticides" target="_blank" >http://www.eurekaselect.com/node/163753/article/oxime-k033-reactivation-activity-of-cholinesterases-inhibited-by-various-nerve-agents-and-organophosphorus-pesticides</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/1570164615666180713112238" target="_blank" >10.2174/1570164615666180713112238</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 &quot;broad spectrum reactivator&quot;. 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 &amp; 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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 &quot;broad spectrum reactivator&quot;. 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 &amp; 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

30107 - Medicinal chemistry

Projekt

<a href="/cs/project/GA18-01734S" target="_blank" >GA18-01734S: Reaktivátory butyrylcholinesterasy pro přípravu pseudo-katalytických scavengerů využitelných při intoxikacích organofosforovými sloučeninami</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Letters in drug design &amp; discovery

ISSN

1570-1808

e-ISSN

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Svazek periodika

15

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

AE - Spojené arabské emiráty

Počet stran výsledku

7

Strana od-do

1124-1130

Kód UT WoS článku

000445684700001

EID výsledku v databázi Scopus

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