Understanding the interaction modes and reactivity of trimedoxime toward mmache inhibited by nerve agents: Theoretical and experimental aspects

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F20%3A50017155" target="_blank" >RIV/62690094:18470/20:50017155 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/20:10417730

Výsledek na webu

<a href="https://www.mdpi.com/1422-0067/21/18/6510" target="_blank" >https://www.mdpi.com/1422-0067/21/18/6510</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms21186510" target="_blank" >10.3390/ijms21186510</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Understanding the interaction modes and reactivity of trimedoxime toward mmache inhibited by nerve agents: Theoretical and experimental aspects

Popis výsledku v původním jazyce

Organophosphorus (OP) compounds are used as both chemical weapons and pesticides. However, these agents are very dangerous and toxic to humans, animals, and the environment. Thus, investigations with reactivators have been deeply developed in order to design new antidotes with better efficiency, as well as a greater spectrum of action in the acetylcholinesterase (AChE) reactivation process. With that in mind, in this work, we investigated the behavior of trimedoxime toward the Mus musculus acetylcholinesterase (MmAChE) inhibited by a range of nerve agents, such as chemical weapons. From experimental assays, reactivation percentages were obtained for the reactivation of different AChE–OP complexes. On the other hand, theoretical calculations were performed to assess the differences in interaction modes and the reactivity of trimedoxime within the AChE active site. Comparing theoretical and experimental data, it is possible to notice that the oxime, in most cases, showed better reactivation percentages at higher concentrations, with the best result for the reactivation of the AChE–VX adduct. From this work, it was revealed that the mechanistic process contributes most to the oxime efficiency than the interaction in the site. In this way, this study is important to better understand the reactivation process through trimedoxime, contributing to the proposal of novel antidotes. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. T.

Název v anglickém jazyce

Understanding the interaction modes and reactivity of trimedoxime toward mmache inhibited by nerve agents: Theoretical and experimental aspects

Popis výsledku anglicky

Organophosphorus (OP) compounds are used as both chemical weapons and pesticides. However, these agents are very dangerous and toxic to humans, animals, and the environment. Thus, investigations with reactivators have been deeply developed in order to design new antidotes with better efficiency, as well as a greater spectrum of action in the acetylcholinesterase (AChE) reactivation process. With that in mind, in this work, we investigated the behavior of trimedoxime toward the Mus musculus acetylcholinesterase (MmAChE) inhibited by a range of nerve agents, such as chemical weapons. From experimental assays, reactivation percentages were obtained for the reactivation of different AChE–OP complexes. On the other hand, theoretical calculations were performed to assess the differences in interaction modes and the reactivity of trimedoxime within the AChE active site. Comparing theoretical and experimental data, it is possible to notice that the oxime, in most cases, showed better reactivation percentages at higher concentrations, with the best result for the reactivation of the AChE–VX adduct. From this work, it was revealed that the mechanistic process contributes most to the oxime efficiency than the interaction in the site. In this way, this study is important to better understand the reactivation process through trimedoxime, contributing to the proposal of novel antidotes. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. T.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

International Journal of Molecular Sciences

ISSN

1422-0067

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

18

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

13

Strana od-do

"Article number 6510"

Kód UT WoS článku

000580260600001

EID výsledku v databázi Scopus

2-s2.0-85090228481