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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,

. 2019 ; 309 (-) : 108682. [pub] 20190601

Language English Country Ireland

Document type Journal Article

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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$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 Synthesis and in vitro evaluation of neutral aryloximes as reactivators of Electrophorus eel acetylcholinesterase inhibited by NEMP, a VX surrogate / $c SFA. Cavalcante, DAS. Kitagawa, RB. Rodrigues, LB. Bernardo, TN. da Silva, WV. Dos Santos, ABA. Correa, JSFD. de Almeida, TCC. França, K. Kuča, ABC. Simas,
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$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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$a Rodrigues, Rafael B $u Brazilian Army Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Avenida das Américas 28705, Rio de Janeiro, 23020-470, Brazil.
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$a Dos Santos, Wellington V $u Emergency and Rescue Department (DSE), Rio de Janeiro State Fire Department (CBMERJ), Praça São Salvador 4, Rio de Janeiro, 22231-170, Brazil; University Universus Veritas (UNIVERITAS), School of Biomedicine, Rua Marquês de Abrantes 55, Rio de Janeiro, 22230-060, Brazil.
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$a Kuča, Kamil $u Department of Chemistry, Faculty of Science, University of Hradec Králové, Rokitanskeho 62, 50003, Hradec Králové, Czech Republic.
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