Assessing the Therapeutic and Toxicological Profile of Novel Acetylcholinesterase Reactivators: Value of In Silico And In Vitro Data

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F23%3A50020584" target="_blank" >RIV/62690094:18470/23:50020584 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.eurekaselect.com/article/126970" target="_blank" >https://www.eurekaselect.com/article/126970</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/0929867330999221014104610" target="_blank" >10.2174/0929867330999221014104610</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Assessing the Therapeutic and Toxicological Profile of Novel Acetylcholinesterase Reactivators: Value of In Silico And In Vitro Data

Popis výsledku v původním jazyce

Organophosphorus compounds (OP) make up an important class of inhibitors, mostly employed as pesticides, even as chemical weapons. These toxic substances act through the inhibition of the acetylcholinesterase (AChE) enzyme, which results in elevated synaptic acetylcholine (ACh) levels, leading to serious adverse effects under the cholinergic syndrome. Many reactivators have been developed to combat the toxic effects of these AChE inhibitors. In this line, the oximes highlight because of their good reactivating power of cholinesterase enzymes. To date, no universal antidotes can reactivate AChE inhibited by any OP agent. This review summarizes the intoxication process by neurotoxic OP agents, along with the development of reactivators capable of reversing their effects, approaching aspects like the therapeutic and toxicological profile of these antidotes. Computational methods and conscious in vitro studies, capable of significantly predicting the toxicological profile of these drug candidates, might support the process of development of these reactivators before entering in vivo studies in animals, and then clinical trials. These approaches can assist in the design of safer and more effective molecules, reducing related cost and time for the process.

Název v anglickém jazyce

Assessing the Therapeutic and Toxicological Profile of Novel Acetylcholinesterase Reactivators: Value of In Silico And In Vitro Data

Popis výsledku anglicky

Organophosphorus compounds (OP) make up an important class of inhibitors, mostly employed as pesticides, even as chemical weapons. These toxic substances act through the inhibition of the acetylcholinesterase (AChE) enzyme, which results in elevated synaptic acetylcholine (ACh) levels, leading to serious adverse effects under the cholinergic syndrome. Many reactivators have been developed to combat the toxic effects of these AChE inhibitors. In this line, the oximes highlight because of their good reactivating power of cholinesterase enzymes. To date, no universal antidotes can reactivate AChE inhibited by any OP agent. This review summarizes the intoxication process by neurotoxic OP agents, along with the development of reactivators capable of reversing their effects, approaching aspects like the therapeutic and toxicological profile of these antidotes. Computational methods and conscious in vitro studies, capable of significantly predicting the toxicological profile of these drug candidates, might support the process of development of these reactivators before entering in vivo studies in animals, and then clinical trials. These approaches can assist in the design of safer and more effective molecules, reducing related cost and time for the process.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Current medicinal chemistry

ISSN

0929-8673

e-ISSN

1875-533X

Svazek periodika

30

Číslo periodika v rámci svazku

36

Stát vydavatele periodika

AE - Spojené arabské emiráty

Počet stran výsledku

18

Strana od-do

4149-4166

Kód UT WoS článku

001028904000005

EID výsledku v databázi Scopus

2-s2.0-85151594267