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 study, we investigated the in vitro AChE inhibitory properties of these hybrids by estimating their IC50 values. Compounds 14 and 15 exhibited inhibitory activity, with IC50 of 226.4 and 24.7 μM respectively. Notably, compound 15 showed a potency comparable to the reference compound pyridostigmine bromide, the only reported drug used prophylactically against nerve agent exposure. These results suggest promissing dual-functional compounds for nerve agent prophylaxis and potential reactivation of enzyme catalytic activity.

Agency for Management and Technological Innovation Brazilian Army Department of Science and Technology Avenida das Américas 28705 23020 470 Rio de Janeiro RJ Brazil

Biomedical Research Center University Hospital Hradec Kralove 50005 Hradec Kralove Czech Republic; Center of Advanced Innovation Technologies VSB Technical University of Ostrava 70800 Ostrava Poruba Czech Republic

Department of Chemistry and Biochemistry Concordia University Montreal QC Canada; Centre for NanoScience Research Concordia University Montreal QC Canada

Institute of Chemical Biological Radiological and Nuclear Defense Avenida das Américas 28705 23020 470 Rio de Janeiro RJ Brazil

Institute of Chemical Biological Radiological and Nuclear Defense Praça General Tibúrcio 80 22290 270 Rio de Janeiro RJ Brazil

Laboratory of Molecular Modeling Applied to Chemical and Biological Defense Praça General Tibúrcio 80 22290 270 Rio de Janeiro RJ Brazil

Laboratory of Molecular Modeling Applied to Chemical and Biological Defense Praça General Tibúrcio 80 22290 270 Rio de Janeiro RJ Brazil; Centre for Basic and Applied Research Faculty of Informatics and Management University of Hradec Kralove 50003 Hradec Kralove Czech Republic

Laboratory Roderick A Barnes Walter Mors Institute of Research on Natural Products CCS Bloco H 21941 902 Rio de Janeiro RJ Brazil

Medical Course Souza Marques College Rio de Janeiro RJ Brazil

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