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Synthesis and in vitro evaluation of neutral aryloximes as reactivators of Electrophorus eel acetylcholinesterase inhibited by NEMP, a VX surrogate
SFA. Cavalcante, DAS. Kitagawa, RB. Rodrigues, LB. Bernardo, TN. da Silva, WV. Dos Santos, ABA. Correa, JSFD. de Almeida, TCC. França, K. Kuča, ABC. Simas,
Language English Country Ireland
Document type Journal Article
- MeSH
- Acetylcholinesterase chemistry metabolism MeSH
- Eels MeSH
- Antidotes chemical synthesis metabolism MeSH
- Cholinesterase Inhibitors chemistry metabolism MeSH
- Organothiophosphorus Compounds chemistry metabolism MeSH
- Oximes chemistry metabolism MeSH
- Pyrrolidines chemistry metabolism MeSH
- Cholinesterase Reactivators chemical synthesis metabolism MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
Casualties caused by nerve agents, potent acetylcholinesterase inhibitors, have attracted attention from media recently. Poisoning with these chemicals may be fatal if not correctly addressed. Therefore, research on novel antidotes is clearly warranted. Pyridinium oximes are the only clinically available compounds, but poor penetration into the blood-brain barrier hampers efficient enzyme reactivation at the central nervous system. In searching for structural factors that may be explored in SAR studies, we synthesized and evaluated neutral aryloximes as reactivators for acetylcholinesterase inhibited by NEMP, a VX surrogate. Although few tested compounds reached comparable reactivation results with clinical standards, they may be considered as leads for further optimization.
Emergency and Rescue Department Praça São Salvador 4 Rio de Janeiro 22231 170 Brazil
University Castelo Branco School of Pharmacy Avenida Santa Cruz 1631 Rio de Janeiro 21710 255 Brazil
Walter Mors Institute of Research on Natural Products CCS Bloco H Rio de Janeiro 21941 902 Brazil
References provided by Crossref.org
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- $a Cavalcante, Samir F de A $u Brazilian Army Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Avenida das Américas 28705, Rio de Janeiro, 23020-470, Brazil; Walter Mors Institute of Research on Natural Products (IPPN), Federal University of Rio de Janeiro (UFRJ), CCS, Bloco H, Rio de Janeiro, 21941-902, Brazil; University Castelo Branco (UCB), School of Pharmacy, Avenida Santa Cruz 1631, Rio de Janeiro, 21710-255, Brazil; Department of Chemistry, Faculty of Science, University of Hradec Králové, Rokitanskeho 62, 50003, Hradec Králové, Czech Republic. Electronic address: samir.cavalcante@eb.mil.br.
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- $a Casualties caused by nerve agents, potent acetylcholinesterase inhibitors, have attracted attention from media recently. Poisoning with these chemicals may be fatal if not correctly addressed. Therefore, research on novel antidotes is clearly warranted. Pyridinium oximes are the only clinically available compounds, but poor penetration into the blood-brain barrier hampers efficient enzyme reactivation at the central nervous system. In searching for structural factors that may be explored in SAR studies, we synthesized and evaluated neutral aryloximes as reactivators for acetylcholinesterase inhibited by NEMP, a VX surrogate. Although few tested compounds reached comparable reactivation results with clinical standards, they may be considered as leads for further optimization.
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