In Vitro Evaluation of Neutral Aryloximes as Reactivators for <em>Electrophorus eel</em> Acetylcholinesterase Inhibited by Paraoxon
Daniel A. S. Kitagawa,
Samir F. de A. Cavalcante,
Reuel L. de Paula,
Rafael B. Rodrigues,
Leandro B. Bernardo,
Munique C. J. da Silva,
Thiago N. da Silva,
Wellington V. dos Santos,
José M. Granjeiro,
Joyce S. F. D. de Almeida,
Marcos C. Barcellos,
Ana Beatriz de A. Correa,
Tanos C. C. França,
Kamil Kuča,
Alessandro B. C. Simas
Affiliations
Daniel A. S. Kitagawa
Laboratory of Molecular Modelling Applied to Chemical and Biological Defense (LMACBD), Military Institute of Engineering (IME), Praça General Tibúrcio 80, Rio de Janeiro 22290-270, Brazil
Samir F. de A. Cavalcante
Brazilian Army Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (CTEx), Avenida das Américas 28705, Rio de Janeiro 23020-470, Brazil
Reuel L. de Paula
Brazilian Army Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (CTEx), Avenida das Américas 28705, Rio de Janeiro 23020-470, Brazil
Rafael B. Rodrigues
Brazilian Army Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (CTEx), Avenida das Américas 28705, Rio de Janeiro 23020-470, Brazil
Leandro B. Bernardo
Brazilian Army Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (CTEx), Avenida das Américas 28705, Rio de Janeiro 23020-470, Brazil
Munique C. J. da Silva
Brazilian Army Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (CTEx), Avenida das Américas 28705, Rio de Janeiro 23020-470, Brazil
Thiago N. da Silva
Castelo Branco University (UCB), School of Pharmacy, Avenida Santa Cruz 1631, Rio de Janeiro 21710-255, Brazil
Wellington V. dos Santos
Emergency and Rescue Department (DSE), Rio de Janeiro State Fire Department (CBMERJ), Praça São Salvador 4, Rio de Janeiro 22231-170, Brazil
José M. Granjeiro
National Institute of Metrology, Standardization and Industrial Quality (INMETRO), Avenida Nossa Senhora das Graças 50, Duque de Caxias 25250-020, Brazil
Joyce S. F. D. de Almeida
Laboratory of Molecular Modelling Applied to Chemical and Biological Defense (LMACBD), Military Institute of Engineering (IME), Praça General Tibúrcio 80, Rio de Janeiro 22290-270, Brazil
Marcos C. Barcellos
Brazilian Army Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (CTEx), Avenida das Américas 28705, Rio de Janeiro 23020-470, Brazil
Ana Beatriz de A. Correa
Brazilian Army Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (CTEx), Avenida das Américas 28705, Rio de Janeiro 23020-470, Brazil
Tanos C. C. França
Laboratory of Molecular Modelling Applied to Chemical and Biological Defense (LMACBD), Military Institute of Engineering (IME), Praça General Tibúrcio 80, Rio de Janeiro 22290-270, Brazil
Kamil Kuča
Department of Chemistry, Faculty of Science, University of Hradec Králové, Rokitanskeho 62, 50003 Hradec Králové, Czech Republic
Alessandro B. C. Simas
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
Casualties caused by organophosphorus pesticides are a burden for health systems in developing and poor countries. Such compounds are potent acetylcholinesterase irreversible inhibitors, and share the toxic profile with nerve agents. Pyridinium oximes are the only clinically available antidotes against poisoning by these substances, but their poor penetration into the blood-brain barrier hampers the efficient enzyme reactivation at the central nervous system. In searching for structural factors that may be explored in future SAR studies, we evaluated neutral aryloximes as reactivators for paraoxon-inhibited Electrophorus eel acetylcholinesterase. Our findings may result into lead compounds, useful for development of more active compounds for emergencies and supportive care.