Novel Group of AChE Reactivators-Synthesis, In Vitro Reactivation and Molecular Docking Study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F18%3A50014798" target="_blank" >RIV/62690094:18470/18:50014798 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/18:10381617 RIV/60162694:G44__/18:43889616

Výsledek na webu

<a href="http://dx.doi.org/10.3390/molecules23092291" target="_blank" >http://dx.doi.org/10.3390/molecules23092291</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules23092291" target="_blank" >10.3390/molecules23092291</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Novel Group of AChE Reactivators-Synthesis, In Vitro Reactivation and Molecular Docking Study

Popis výsledku v původním jazyce

The acetylcholinesterase (AChE) reactivators (e.g., obidoxime, asoxime) became an essential part of organophosphorus (OP) poisoning treatment, together with atropine and diazepam. They are referred to as a causal treatment of OP poisoning, because they are able to split the OP moiety from AChE active site and thus renew its function. In this approach, fifteen novel AChE reactivators were determined. Their molecular design originated from former K-oxime compounds K048 and K074 with remaining oxime part of the molecule and modified part with heteroarenium moiety. The novel compounds were prepared, evaluated in vitro on human AChE (HssAChE) inhibited by tabun, paraoxon, methylparaoxon or DFP and compared to commercial HssAChE reactivators (pralidoxime, methoxime, trimedoxime, obidoxime, asoxime) or previously prepared compounds (K048, K074, K075, K203). Some of presented oxime reactivators showed promising ability to reactivate HssAChE comparable or higher than the used standards. The molecular modelling study was performed with one compound that presented the ability to reactivate GA-inhibited HssAChE. The SAR features concerning the heteroarenium part of the reactivator&apos;s molecule are described.

Název v anglickém jazyce

Novel Group of AChE Reactivators-Synthesis, In Vitro Reactivation and Molecular Docking Study

Popis výsledku anglicky

The acetylcholinesterase (AChE) reactivators (e.g., obidoxime, asoxime) became an essential part of organophosphorus (OP) poisoning treatment, together with atropine and diazepam. They are referred to as a causal treatment of OP poisoning, because they are able to split the OP moiety from AChE active site and thus renew its function. In this approach, fifteen novel AChE reactivators were determined. Their molecular design originated from former K-oxime compounds K048 and K074 with remaining oxime part of the molecule and modified part with heteroarenium moiety. The novel compounds were prepared, evaluated in vitro on human AChE (HssAChE) inhibited by tabun, paraoxon, methylparaoxon or DFP and compared to commercial HssAChE reactivators (pralidoxime, methoxime, trimedoxime, obidoxime, asoxime) or previously prepared compounds (K048, K074, K075, K203). Some of presented oxime reactivators showed promising ability to reactivate HssAChE comparable or higher than the used standards. The molecular modelling study was performed with one compound that presented the ability to reactivate GA-inhibited HssAChE. The SAR features concerning the heteroarenium part of the reactivator&apos;s molecule are described.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

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

Molecules

ISSN

1420-3049

e-ISSN

—

Svazek periodika

23

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

16

Strana od-do

1-16

Kód UT WoS článku

000447365100202

EID výsledku v databázi Scopus

2-s2.0-85053068422