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Are the current commercially available oximes capable of reactivating acetylcholinesterase inhibited by the nerve agents of the A-series?
Santos, Marcelo C; Botelho, Fernanda D; Gonçalves, Arlan S; Kitagawa, Daniel A S; Borges, Caio V N; Carvalho-Silva, Taynara; Bernardo, Leandro B; Ferreira, Cíntia N; Rodrigues, Rafael B; Ferreira Neto, Denise C; Nepovimova, Eugenie; Kuca, Kamil; LaPlante, Steven R; Lima, Antonio L S; França, Tanos C C; Cavalcante, Samir F A.
Afiliação
  • Santos MC; Laboratory of Molecular Modeling Applied to Chemical and Biological Defense, Military Institute of Engineering, Rio de Janeiro, Brazil.
  • Botelho FD; Laboratory of Molecular Modeling Applied to Chemical and Biological Defense, Military Institute of Engineering, Rio de Janeiro, Brazil.
  • Gonçalves AS; Federal Institute of Education, Science and Technology of Espírito Santo - Units Vila Velha and Vitória, Vitória, ES, Brazil.
  • Kitagawa DAS; Federal University of Espírito Santo, Unit Goiabeiras, Vitória, ES, Brazil.
  • Borges CVN; Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (CTEx), Rio de Janeiro, Brazil.
  • Carvalho-Silva T; Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (CTEx), Rio de Janeiro, Brazil.
  • Bernardo LB; Chemical Engineering Department, Military Institute of Engineering, Rio de Janeiro, Brazil.
  • Ferreira CN; Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (CTEx), Rio de Janeiro, Brazil.
  • Rodrigues RB; Chemical Engineering Department, Military Institute of Engineering, Rio de Janeiro, Brazil.
  • Ferreira Neto DC; Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (CTEx), Rio de Janeiro, Brazil.
  • Nepovimova E; Chemical Engineering Department, Military Institute of Engineering, Rio de Janeiro, Brazil.
  • Kuca K; Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (CTEx), Rio de Janeiro, Brazil.
  • LaPlante SR; Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (CTEx), Rio de Janeiro, Brazil.
  • Lima ALS; Chemical Engineering Department, Military Institute of Engineering, Rio de Janeiro, Brazil.
  • França TCC; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic.
  • Cavalcante SFA; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic.
Arch Toxicol ; 96(9): 2559-2572, 2022 09.
Article em En | MEDLINE | ID: mdl-35666269
The misuse of novichok agents in assassination attempts has been reported in the international media since 2018. These relatively new class of neurotoxic agents is claimed to be more toxic than the agents of the G and V series and so far, there is no report yet in literature about potential antidotes against them. To shed some light into this issue, we report here the design and synthesis of NTMGMP, a surrogate of A-242 and also the first surrogate of a novichok agent useful for experimental evaluation of antidotes. Furthermore, the efficiency of the current commercial oximes to reactivate NTMGMP-inhibited acetylcholinesterase (AChE) was evaluated. The Ellman test was used to confirm the complete inhibition of AChE, and to compare the subsequent rates of reactivation in vitro as well as to evaluate aging. In parallel, molecular docking, molecular dynamics and MM-PBSA studies were performed on a computational model of the human AChE (HssAChE)/NTMGMP complex to assess the reactivation performances of the commercial oximes in silico. Experimental and theoretical studies matched the exact hierarchy of efficiency and pointed to trimedoxime as the most promising commercial oxime for reactivation of AChE inhibited by A-242.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Reativadores da Colinesterase / Agentes Neurotóxicos Limite: Humans Idioma: En Revista: Arch Toxicol Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Alemanha
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Reativadores da Colinesterase / Agentes Neurotóxicos Limite: Humans Idioma: En Revista: Arch Toxicol Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Alemanha