In vitro evaluation of isatin-pyridine oxime hybrids as potential acetylcholinesterase inhibitors for nerve agent prophylaxis.

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.