biostudies-literatureDa Silva ODirection G??n??rale de l&apos;ArmementAgence Nationale de la RechercheR??gion NormandieService de Sant?? des Arm??eMinist??re des Arm??esUniversit?? de RouenConseil R??gional Hauts-de-FranceEuropean Regional Development Fund4649-4666https://www.ebi.ac.uk/biostudies/studies/S-EPMC8958973biostudies-literatureUnknown65(6)Recent events demonstrated that organophosphorus nerve agents are a serious threat for civilian and military populations. The current therapy includes a pyridinium aldoxime reactivator to restore the enzymatic activity of acetylcholinesterase located in the central nervous system and neuro-muscular junctions. One major drawback of these charged acetylcholinesterase reactivators is their poor ability to cross the blood-brain barrier. In this study, we propose to evaluate glucoconjugated oximes devoid of permanent charge as potential central nervous system reactivators. We determined their <i>in vitro</i> reactivation efficacy on inhibited human acetylcholinesterase, the crystal structure of two compounds in complex with the enzyme, their protective index on intoxicated mice, and their pharmJournal of medicinal chemistryA New Class of Bi- and Trifunctional Sugar Oximes as Antidotes against Organophosphorus Poisoning.PMC8958973ANR-13-ASTR-0002ANR-17-CE39-0012NBC-5-C-4210ANR-18-EURE-0020 XL CHEMANR-11-LABX-0029Calas AGCoisne CGastellier AJBaati RNachon FProbst NWarnault PLandry CDehouck MPTrancart MJean LCourageux CRenard PYDa Silva OHanak ASGosselet FDias JfalseA New Class of Bi- and Trifunctional Sugar Oximes as Antidotes against Organophosphorus Poisoning.Recent events demonstrated that organophosphorus nerve agents are a serious threat for civilian and military populations. The current therapy includes a pyridinium aldoxime reactivator to restore the enzymatic activity of acetylcholinesterase located in the central nervous system and neuro-muscular junctions. One major drawback of these charged acetylcholinesterase reactivators is their poor ability to cross the blood-brain barrier. In this study, we propose to evaluate glucoconjugated oximes devoid of permanent charge as potential central nervous system reactivators. We determined their <i>in vitro</i> reactivation efficacy on inhibited human acetylcholinesterase, the crystal structure of two compounds in complex with the enzyme, their protective index on intoxicated mice, and their pharm2022-01-01T00:00:00Z2022 Mar2026-05-09T13:46:12.205Z2025-02-18T23:44:37.73ZS-EPMC89589733525520910.1021/acs.jmedchem.1c01748