Da Silva_2022_J.Med.Chem_65_4649

Reference

Title : A New Class of Bi- and Trifunctional Sugar Oximes as Antidotes against Organophosphorus Poisoning - Da Silva_2022_J.Med.Chem_65_4649
Author(s) : Da Silva O , Probst N , Landry C , Hanak AS , Warnault P , Coisne C , Calas AG , Gosselet F , Courageux C , Gastellier AJ , Trancart M , Baati R , Dehouck MP , Jean L , Nachon F , Renard PY , Dias J
Ref : Journal of Medicinal Chemistry , 65 :4649 , 2022
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.
ESTHER : Da Silva_2022_J.Med.Chem_65_4649
PubMedSearch : Da Silva_2022_J.Med.Chem_65_4649
PubMedID: 35255209
Gene_locus related to this paper: human-ACHE

Related information

Gene_locus related to this paper: human-ACHE

Citations formats

Da Silva O, Probst N, Landry C, Hanak AS, Warnault P, Coisne C, Calas AG, Gosselet F, Courageux C, Gastellier AJ, Trancart M, Baati R, Dehouck MP, Jean L, Nachon F, Renard PY, Dias J (2022)
A New Class of Bi- and Trifunctional Sugar Oximes as Antidotes against Organophosphorus Poisoning
Journal of Medicinal Chemistry 65 :4649

Da Silva O, Probst N, Landry C, Hanak AS, Warnault P, Coisne C, Calas AG, Gosselet F, Courageux C, Gastellier AJ, Trancart M, Baati R, Dehouck MP, Jean L, Nachon F, Renard PY, Dias J (2022)
Journal of Medicinal Chemistry 65 :4649