Review about Structure and Evaluation of Reactivators of Acetylcholinesterase Inhibited with Neurotoxic Organophosphorus Compounds

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F21%3A50018048" target="_blank" >RIV/62690094:18470/21:50018048 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.ingentaconnect.com/contentone/ben/cmc/2021/00000028/00000007/art00009" target="_blank" >https://www.ingentaconnect.com/contentone/ben/cmc/2021/00000028/00000007/art00009</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/0929867327666200425213215" target="_blank" >10.2174/0929867327666200425213215</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Review about Structure and Evaluation of Reactivators of Acetylcholinesterase Inhibited with Neurotoxic Organophosphorus Compounds

Popis výsledku v původním jazyce

Background: Neurotoxic chemical warfare agents can be classified as some of the most dangerous chemicals for humanity. The most effective of those agents are the Organophosphates (OPs) capable of restricting the enzyme Acetylcholinesterase (AChE), which in turn, controls the nerve impulse transmission. When AChE is inhibited by OPs, its reactivation can be usually performed through cationic oximes. However, until today, it has not been developed one universal defense agent, with complete effective reactivation activity for AChE inhibited by any of the many types of existing neurotoxic OPs. For this reason, before treating people intoxicated by an OP, it is necessary to determine the neurotoxic compound that was used for contamination, in order to select the most effective oxime. Unfortunately, this task usually requires a relatively long time, raising the possibility of death. Cationic oximes also display a limited capacity of permeating the Blood-Brain Barrier (BBB). This fact compromises their capacity to reactivating AChE inside the nervous system. Methods: We performed a comprehensive search on the data about OPs available on the scientific literature today in order to cover all the main drawbacks still faced in the research for the development of effective antidotes against those compounds. Results: Therefore, this review about neurotoxic OPs and the reactivation of AChE, provides insights for the new agents&apos; development. The most expected defense agent is a molecule without toxicity and effective to reactivate AChE inhibited by all neurotoxic OPs. Conclusion: To develop these new agents, the application of diverse scientific areas of research, especially theoretical procedures as computational science (computer simulation, docking and dynamics), organic synthesis, spectroscopic methodologies, biology, biochemical and biophysical information, medicinal chemistry, pharmacology and toxicology, is necessary.

Název v anglickém jazyce

Review about Structure and Evaluation of Reactivators of Acetylcholinesterase Inhibited with Neurotoxic Organophosphorus Compounds

Popis výsledku anglicky

Background: Neurotoxic chemical warfare agents can be classified as some of the most dangerous chemicals for humanity. The most effective of those agents are the Organophosphates (OPs) capable of restricting the enzyme Acetylcholinesterase (AChE), which in turn, controls the nerve impulse transmission. When AChE is inhibited by OPs, its reactivation can be usually performed through cationic oximes. However, until today, it has not been developed one universal defense agent, with complete effective reactivation activity for AChE inhibited by any of the many types of existing neurotoxic OPs. For this reason, before treating people intoxicated by an OP, it is necessary to determine the neurotoxic compound that was used for contamination, in order to select the most effective oxime. Unfortunately, this task usually requires a relatively long time, raising the possibility of death. Cationic oximes also display a limited capacity of permeating the Blood-Brain Barrier (BBB). This fact compromises their capacity to reactivating AChE inside the nervous system. Methods: We performed a comprehensive search on the data about OPs available on the scientific literature today in order to cover all the main drawbacks still faced in the research for the development of effective antidotes against those compounds. Results: Therefore, this review about neurotoxic OPs and the reactivation of AChE, provides insights for the new agents&apos; development. The most expected defense agent is a molecule without toxicity and effective to reactivate AChE inhibited by all neurotoxic OPs. Conclusion: To develop these new agents, the application of diverse scientific areas of research, especially theoretical procedures as computational science (computer simulation, docking and dynamics), organic synthesis, spectroscopic methodologies, biology, biochemical and biophysical information, medicinal chemistry, pharmacology and toxicology, is necessary.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

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

2021

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

—

Svazek periodika

28

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

AE - Spojené arabské emiráty

Počet stran výsledku

21

Strana od-do

1422-1442

Kód UT WoS článku

000640182300008

EID výsledku v databázi Scopus

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