Aim: Organophosphorus compounds are irreversible inhibitors of AChE. Without immediate countermeasure, intoxication leads quickly to death. None of the clinically-used causal antidotes can ensure a good prognosis for any poisoned patient. When fallen into the wrong hands, organophosphates represent a serious threat to mankind. Results & methodology: Herein, we describe two novel compounds as unique merged molecules built on a tacrine scaffold against organophosphorus intoxication. These reactivators of AChE have balanced physicochemical properties, and should be able to cross the blood-brain barrier with a slightly lowered cytotoxicity profile compared to reference tacrine. Conclusion: Their efficiency compared with pralidoxime and obidoxime was proved against dichlorvos.
Keywords: acetylcholinesterase; dichlorvos; nerve agent; organophosphorus; oxime reactivator; pesticide; tacrine.