Organophosphorus poisoning caused by some pesticides and nerve agents is a life-threating condition that must be swiftly addressed to avoid casualties. Despite the availability of medical countermeasures, the clinically available compounds lack a broad spectrum, are not effective towards all organophosphorus toxins, and have poor pharmacokinetics properties to allow them crossing the blood-brain barrier, hampering cholinesterase reactivation at the central nervous system. In this work, we designed and synthesised novel isatin derivatives, linked to a pyridinium 4-oxime moiety by an alkyl chain with improved calculated properties, and tested their reactivation potency against paraoxon- and NEMP-inhibited acetylcholinesterase in comparison to the standard antidote pralidoxime. Our results showed that these compounds displayed comparable in vitro reactivation also pointed by the in silico studies, suggesting that they are promising compounds to tackle organophosphorus poisoning.

Brazilian Army Technological Center Rio de Janeiro Brazil

Department of Chemistry Faculty of Science University of Hradec Králové Hradec Králové Czech Republic

Emergency and Rescue Department Rio de Janeiro Brazil

Instituto de Pesquisas de Produtos Naturais Walter Mors Rio de Janeiro Brazil

Instituto Federal de Educação Ciência e Tecnologia do Rio de Janeiro Nilópolis Brazil

Laboratory of Molecular Modelling Applied to Chemical and Biological Defense Rio de Janeiro Brazil

School of Pharmacy Universidade Castelo Branco Rio de Janeiro Brazil

Universidade Estácio de Sá Rio de Janeiro Brazil

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