Skip to Main content Skip to Navigation
Journal articles

A New Class of Bi- and Trifunctional Sugar Oximes as Antidotes against Organophosphorus Poisoning

Abstract : 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 in vitro 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 pharmacokinetics. We then evaluated their endothelial permeability coefficients with a human in vitro model. This study shed light on the structural restrains of new sugar oximes designed to reach the central nervous system through the glucose transporter located at the blood–brain barrier.
Document type :
Journal articles
Complete list of metadata

https://hal-univ-artois.archives-ouvertes.fr/hal-03706969
Contributor : Virginie Justin-Labonne Connect in order to contact the contributor
Submitted on : Tuesday, July 19, 2022 - 5:54:01 PM
Last modification on : Thursday, August 4, 2022 - 10:09:02 AM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : 2022-09-07

Please log in to resquest access to the document

Identifiers

Citation

Ophélie da Silva, Nicolas Probst, Christophe Landry, Anne-Sophie Hanak, Pierre Warnault, et al.. A New Class of Bi- and Trifunctional Sugar Oximes as Antidotes against Organophosphorus Poisoning. Journal of Medicinal Chemistry, American Chemical Society, 2022, 65 (6), pp.4649-4666. ⟨10.1021/acs.jmedchem.1c01748⟩. ⟨hal-03706969⟩

Share

Metrics