title: Phenyltetrahydroisoquinoline-pyridinaldoxime conjugates as efficient uncharged reactivators for the dephosphylation of inhibited human acetylcholinesterase.
abstract: Pyridinium and bis-pyridinium aldoximes are used as antidotes to reactivate acetylcholinesterase (AChE) inhibited by organophosphorus nerve agents. Herein, we described a series of nine nonquaternary phenyltetrahydroisoquinoline-pyridinaldoxime conjugates more efficient than or as efficient as pyridinium oximes to reactivate VX-, tabun- and ethyl paraoxon-inhibited human AChE. This study explores the structure-activity relationships of this new family of reactivators and shows that 1b-d are uncharged hAChE reactivators with a broad spectrum.
authors.affiliation: Université de Rouen, COBRA CNRS UMR 6014 and FR 3038, IRCOF, 1 Rue Tesnière, 76821 Mont St. Aignan Cedex, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Mercey
authors.forename: Julien
authors.initials: J
authors.lastname: Renou
authors.forename: Tristan
authors.initials: T
authors.lastname: Verdelet
authors.forename: Maria
authors.initials: M
authors.lastname: Kliachyna
authors.forename: Rachid
authors.initials: R
authors.lastname: Baati
authors.forename: Emilie
authors.initials: E
authors.lastname: Gillon
authors.forename: Mélanie
authors.initials: M
authors.lastname: Arboléas
authors.forename: Mélanie
authors.initials: M
authors.lastname: Loiodice
authors.forename: Florian
authors.initials: F
authors.lastname: Nachon
authors.forename: Ludovic
authors.initials: L
authors.lastname: Jean
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Renard
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004793:Enzyme Reactivators / Q000494:pharmacology*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D010091:Oximes / Q000494:pharmacology*; D010766:Phosphorylation
chemical_list: D002800:Cholinesterase Inhibitors; D004793:Enzyme Reactivators; D007546:Isoquinolines; D010091:Oximes; C578476:phenyltetrahydroisoquinoline-pyridinaldoxime; D000110:Acetylcholinesterase