1 Laboratory of Molecular Modeling Applied to Chemical and Biological Defense, Military Institute of Engineering, Rio de Janeiro, 22290-270, RJ, Brazil.
2 Department of Chemistry and Biochemistry, Concordia University, Montreal, H4B 1R6, QC, Canada.
3 School of Health, Concordia University, Montreal, Quebec, H4B 1R6, QC, Canada.
4 Centre for Nanoscience Research (CeNSR), Concordia University, Montreal, H4B 1R6, QC, Canada.
5 Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (CTEx), Rio de Janeiro, 23020-470, RJ, Brazil.
6 Agency for Technology Management and Innovation (AGITEC), Rio de Janeiro, 23020-470, RJ, Brazil.
7 Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (CTEx), Rio de Janeiro, 23020-470, RJ, Brazil. samir.cavalcante@eb.mil.br.
8 Center for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Kralove, 50003, Hradec Kralove, Czech Republic. samir.cavalcante@eb.mil.br.
9 Centre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique (INRS), Laval, H7V 1B7, QC, Canada.
10 PROTEO, the Quebec Network for Research on Protein Function, Engineering, and Applications, Université Laval, Quebec, G1V 0A6, QC, Canada.
11 Laboratory of Molecular Modeling Applied to Chemical and Biological Defense, Military Institute of Engineering, Rio de Janeiro, 22290-270, RJ, Brazil. tanos@ime.eb.br.
12 Center for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Kralove, 50003, Hradec Kralove, Czech Republic. tanos@ime.eb.br.
13 Centre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique (INRS), Laval, H7V 1B7, QC, Canada. tanos@ime.eb.br.
14 PROTEO, the Quebec Network for Research on Protein Function, Engineering, and Applications, Université Laval, Quebec, G1V 0A6, QC, Canada. tanos@ime.eb.br.

Three new isatin-pyridine-2-oxime hybrids (AM01-03) were synthesized and experimentally evaluated as reactivators of acetylcholinesterase (AChE) inhibited by a surrogate of the nerve agent A-242, in comparison with their 4-oxime isomers previously reported by our research group. Furthermore, the interactions of these molecules within the AChE/A-242 complex were assessed through docking and molecular dynamics (MD) simulations. Our results show that the 2-oxime isomers, unlike their 4-oxime analogues, can reactivate AChE inhibited by the A-242 surrogate at 100 µM and are even capable of outperforming the commercial reactivator HI-6. These findings suggest that isatin-oxime hybrids may exhibit a specific biological activity-similar to that observed for obidoxime and trimedoxime-in the reactivation of AChE inhibited by A-242.