Oxime-mediated in vitro reactivation kinetic analysis of organophosphates-inhibited human and electric eel acetylcholinesterase

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F16%3A50004737" target="_blank" >RIV/62690094:18470/16:50004737 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/16:10330362

Výsledek na webu

<a href="http://www.tandfonline.com/doi/abs/10.3109/15376516.2016.1143070?journalCode=itxm20" target="_blank" >http://www.tandfonline.com/doi/abs/10.3109/15376516.2016.1143070?journalCode=itxm20</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3109/15376516.2016.1143070" target="_blank" >10.3109/15376516.2016.1143070</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Oxime-mediated in vitro reactivation kinetic analysis of organophosphates-inhibited human and electric eel acetylcholinesterase

Popis výsledku v původním jazyce

Organophosphate (OP)-based pesticides and nerve agents are highly toxic compounds which interrupt the catalytic mechanism of acetylcholinesterase (AChE) by phosphorylating the hydroxyl moiety of serine residue. The inhibited enzyme can be reactivated by the nucleophilic action of oxime reactivators. To analyze the effect of different AChE sources on reactivation efficacy of reactivators, several in vivo studies have carried out using variety of AChE sources like pig, rat and monkey. Investigations on species differences provide a better insight for the development of new reactivators. Hence, present study was mainly targeted on comparative analysis of the reactivation of electric eel and human AChE inhibited by different OP. A series of butene-linked bis-pyridinium mono oximes which vary in functional groups present at the second pyridinium ring have been examined against sarin, VX, tabun and ethyl-paraoxon-poisoned AChE. In case of tabun-inhibited AChEs, tested oximes were better than reference oximes. For VX-poisoned human AChE, reactivator K251 (k(r2);1.51mM(-1)min(-1)) showed good reactivation efficacy with standard oximes. Studies stipulated that butene-linked oximes consisting of different functional moieties are good reactivators and found to have better efficacy to reactivate nerve agent-inhibited human AChE in comparison to eel AChE.

Název v anglickém jazyce

Oxime-mediated in vitro reactivation kinetic analysis of organophosphates-inhibited human and electric eel acetylcholinesterase

Popis výsledku anglicky

Organophosphate (OP)-based pesticides and nerve agents are highly toxic compounds which interrupt the catalytic mechanism of acetylcholinesterase (AChE) by phosphorylating the hydroxyl moiety of serine residue. The inhibited enzyme can be reactivated by the nucleophilic action of oxime reactivators. To analyze the effect of different AChE sources on reactivation efficacy of reactivators, several in vivo studies have carried out using variety of AChE sources like pig, rat and monkey. Investigations on species differences provide a better insight for the development of new reactivators. Hence, present study was mainly targeted on comparative analysis of the reactivation of electric eel and human AChE inhibited by different OP. A series of butene-linked bis-pyridinium mono oximes which vary in functional groups present at the second pyridinium ring have been examined against sarin, VX, tabun and ethyl-paraoxon-poisoned AChE. In case of tabun-inhibited AChEs, tested oximes were better than reference oximes. For VX-poisoned human AChE, reactivator K251 (k(r2);1.51mM(-1)min(-1)) showed good reactivation efficacy with standard oximes. Studies stipulated that butene-linked oximes consisting of different functional moieties are good reactivators and found to have better efficacy to reactivate nerve agent-inhibited human AChE in comparison to eel AChE.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

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Projekt

<a href="/cs/project/LH13009" target="_blank" >LH13009: Výzkum modifikovaných reaktivátorů cholinesteras pro léčbu intoxikací organofosforovými pesticidy</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Toxicology mechanisms and methods

ISSN

1537-6516

e-ISSN

—

Svazek periodika

26

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

319-326

Kód UT WoS článku

000380053100002

EID výsledku v databázi Scopus

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