Reactivation potency of two novel oximes (K456 and K733) against paraoxon-inhibited acetyl and butyrylcholinesterase: In silico and in vitro models

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F19%3A50015699" target="_blank" >RIV/62690094:18470/19:50015699 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/19:10397236

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0009279719300328?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0009279719300328?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.cbi.2019.108735" target="_blank" >10.1016/j.cbi.2019.108735</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Reactivation potency of two novel oximes (K456 and K733) against paraoxon-inhibited acetyl and butyrylcholinesterase: In silico and in vitro models

Popis výsledku v původním jazyce

Organophosphates (OPs) irreversibly inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The reactivation of these inhibited enzymes is paramount for their normal function. Present study evaluates reactivation potency of two newly developed oximes, K456 and K733, against paraoxon (PDX)-inhibited human-RBC-AChE and human-plasma-BChE in comparison to reported reactivator, pralidoxime (2-PAM). In vitro studies showed higher intrinsic toxicities of both oximes than 2-PAM for AChE. No substantial reactivation of hBChE was noted by tested concentration. Contrary to 2-PAM, the in silico study predicted lower binding free energies for both oximes. However, the detailed interaction study revealed inability of oximes to interact with catalytic anionic site of AChE and hBChE in contrast to 2-PAM. Both in vitro and in silico studies conclude that K456 and K733 are unlikely to be used as reactivators of paraoxon-inhibited AChE or BChE.

Název v anglickém jazyce

Reactivation potency of two novel oximes (K456 and K733) against paraoxon-inhibited acetyl and butyrylcholinesterase: In silico and in vitro models

Popis výsledku anglicky

Organophosphates (OPs) irreversibly inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The reactivation of these inhibited enzymes is paramount for their normal function. Present study evaluates reactivation potency of two newly developed oximes, K456 and K733, against paraoxon (PDX)-inhibited human-RBC-AChE and human-plasma-BChE in comparison to reported reactivator, pralidoxime (2-PAM). In vitro studies showed higher intrinsic toxicities of both oximes than 2-PAM for AChE. No substantial reactivation of hBChE was noted by tested concentration. Contrary to 2-PAM, the in silico study predicted lower binding free energies for both oximes. However, the detailed interaction study revealed inability of oximes to interact with catalytic anionic site of AChE and hBChE in contrast to 2-PAM. Both in vitro and in silico studies conclude that K456 and K733 are unlikely to be used as reactivators of paraoxon-inhibited AChE or BChE.

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

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

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Chemico-biological interactions

ISSN

0009-2797

e-ISSN

—

Svazek periodika

310

Číslo periodika v rámci svazku

1.9.2019

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

9

Strana od-do

1-9

Kód UT WoS článku

000482179600019

EID výsledku v databázi Scopus

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