Review about Structure and Evaluation of Reactivators of Acetylcholinesterase Inhibited with Neurotoxic Organophosphorus Compounds.
Acetylcholinesterase
chemical defense
neurotoxic organophosphorus compounds
oximes
reactivators
warfare agents
Journal
Current medicinal chemistry
ISSN: 1875-533X
Titre abrégé: Curr Med Chem
Pays: United Arab Emirates
ID NLM: 9440157
Informations de publication
Date de publication:
2021
2021
Historique:
received:
12
11
2019
revised:
08
03
2020
accepted:
01
04
2020
pubmed:
27
4
2020
medline:
5
5
2021
entrez:
27
4
2020
Statut:
ppublish
Résumé
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. 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. Therefore, this review about neurotoxic OPs and the reactivation of AChE, provides insights for the new agents' development. The most expected defense agent is a molecule without toxicity and effective to reactivate AChE inhibited by all neurotoxic OPs. 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.
Sections du résumé
BACKGROUND
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
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
RESULTS
Therefore, this review about neurotoxic OPs and the reactivation of AChE, provides insights for the new agents' development. The most expected defense agent is a molecule without toxicity and effective to reactivate AChE inhibited by all neurotoxic OPs.
CONCLUSION
CONCLUSIONS
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.
Identifiants
pubmed: 32334495
pii: CMC-EPUB-106117
doi: 10.2174/0929867327666200425213215
doi:
Substances chimiques
Cholinesterase Inhibitors
0
Cholinesterase Reactivators
0
Organophosphorus Compounds
0
Oximes
0
Acetylcholinesterase
EC 3.1.1.7
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1422-1442Informations de copyright
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