1 Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (CTEx), Avenida das Américas 28705, 23020-470, Rio de Janeiro, RJ, Brazil; Laboratory of Molecular Modeling Applied to Chemical and Biological Defense (LMACBD), Military Institute of Engineering (IME), Praça General Tibúrcio 80, 22290-270, Rio de Janeiro, RJ, Brazil. Electronic address: cristina.munique@eb.mil.br.
2 Laboratory of Molecular Modeling Applied to Chemical and Biological Defense (LMACBD), Military Institute of Engineering (IME), Praça General Tibúrcio 80, 22290-270, Rio de Janeiro, RJ, Brazil. Electronic address: amanda.moraes@ime.eb.br.
3 Medical Course, Souza Marques College (FSM), Rio de Janeiro, RJ, Brazil. Electronic address: marianabalthar@gmail.com.
4 Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (CTEx), Avenida das Américas 28705, 23020-470, Rio de Janeiro, RJ, Brazil. Electronic address: anabeatriz.correa@eb.mil.br.
5 Department of Chemistry and Biochemistry, Concordia University, Montreal, QC, Canada. Electronic address: dipanjan.bhattacharyya@concordia.ca.
6 Laboratory Roderick A. Barnes, Walter Mors Institute of Research on Natural Products (IPPN), Federal University of Rio de Janeiro (UFRJ), CCS, Bloco H, 21941-902, Rio de Janeiro, RJ, Brazil. Electronic address: abcsimas@ippn.ufrj.br.
7 Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, 50003, Hradec Kralove, Czech Republic. Electronic address: kamil.kuca@uhk.cz.
8 Department of Chemistry and Biochemistry, Concordia University, Montreal, QC, Canada. Electronic address: pat.forgione@concordia.ca.
9 Laboratory of Molecular Modeling Applied to Chemical and Biological Defense (LMACBD), Military Institute of Engineering (IME), Praça General Tibúrcio 80, 22290-270, Rio de Janeiro, RJ, Brazil; Center for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Kralove, 50003 Hradec Kralove, Czech Republic. Electronic address: tanos@ime.eb.br.
10 Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (CTEx), Avenida das Américas 28705, 23020-470, Rio de Janeiro, RJ, Brazil. Electronic address: samir.cavalcante@eb.mil.br.
11 Agency for Management and Technological Innovation (AGITEC), Brazilian Army Department of Science and Technology, Avenida das Américas 28705, 23020-470, Rio de Janeiro, RJ, Brazil. Electronic address: kitagawa.daniel@eb.mil.br.

Given the recent deployment of nerve agents as a method of warfare and in targeted assassinations, the development of robust, broad-spectrum medical countermeasures is essential. Our research group has synthesized isatin-pyridine oxime hybrids that have previously demonstrated the ability to rescue Electrophorus eel acetylcholinesterase (EeAChE) inhibited by nerve agent surrogates. In this work, we investigate the in vitro AChE inhibitory properties of these hybrids, estimating their IC₅₀. Compounds 14 and 15 evidenced inhibitiory ability (226.4 and 24.7 µM of IC₅₀, respectively), and this last was similar to compound reference pyridostigmine bromide, the only reported drug used as prophylactic measure for nerve agent exposure. Results suggest promisor dual-functional compounds for nerve agent prophylaxis and the reactivation of enzyme catalytic activity.