Oxime K074-in vitro and in silico reactivation of acetylcholinesterase inhibited by nerve agents and pesticides
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F20%3A10412769" target="_blank" >RIV/00179906:_____/20:10412769 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/62690094:18470/20:50014717 RIV/60162694:G44__/20:00555814 RIV/62690094:18450/20:50014717
Výsledek na webu
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=tDYEx7L4Od" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=tDYEx7L4Od</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1080/15569543.2018.1485702" target="_blank" >10.1080/15569543.2018.1485702</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Oxime K074-in vitro and in silico reactivation of acetylcholinesterase inhibited by nerve agents and pesticides
Popis výsledku v původním jazyce
Oxime K074 was formerly considered to be a lead structure for design of novel oximes for reactivation of tabun-inhibited acetylcholinesterase (AChE). In this study, we are summarizing its reactivation activity in case of other nerve agents (sarin, cyclosarin, VX and Russian VX) and pesticides (chlorpyrifos, methylchlorpyrifos and DDVP). For this purpose, standard in vitro method using rat brain homogenate was used. As resulted, oxime K074 was able to reactivate brain ChE (cholinesterases) inhibited by all used nerve agents and pesticides excluding cyclosarin-inhibited ChE. Only slight modification in structure of sarin (isopropyl moiety) and cyclosarin (cyclohexyl moiety) caused extraordinary differences in the reactivation of acetylcholinesterase inhibited by these nerve agents. Obtained molecular docking results suggest that the oxime K074 interacts very well with the inhibitors addressed in this work, and the data obtained by the QM/MM approach showed a good correlation with our experimental results of reactivation rate (%) by the oxime K074.
Název v anglickém jazyce
Oxime K074-in vitro and in silico reactivation of acetylcholinesterase inhibited by nerve agents and pesticides
Popis výsledku anglicky
Oxime K074 was formerly considered to be a lead structure for design of novel oximes for reactivation of tabun-inhibited acetylcholinesterase (AChE). In this study, we are summarizing its reactivation activity in case of other nerve agents (sarin, cyclosarin, VX and Russian VX) and pesticides (chlorpyrifos, methylchlorpyrifos and DDVP). For this purpose, standard in vitro method using rat brain homogenate was used. As resulted, oxime K074 was able to reactivate brain ChE (cholinesterases) inhibited by all used nerve agents and pesticides excluding cyclosarin-inhibited ChE. Only slight modification in structure of sarin (isopropyl moiety) and cyclosarin (cyclohexyl moiety) caused extraordinary differences in the reactivation of acetylcholinesterase inhibited by these nerve agents. Obtained molecular docking results suggest that the oxime K074 interacts very well with the inhibitors addressed in this work, and the data obtained by the QM/MM approach showed a good correlation with our experimental results of reactivation rate (%) by the oxime K074.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30108 - Toxicology
Návaznosti výsledku
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
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2020
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Toxin Reviews
ISSN
1556-9543
e-ISSN
—
Svazek periodika
39
Číslo periodika v rámci svazku
2
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
10
Strana od-do
157-166
Kód UT WoS článku
000532601200007
EID výsledku v databázi Scopus
2-s2.0-85052100595