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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Renou, Julien Mercey, Guillaume Verdelet, Tristan Paunescu, Emilia Gillon, Emilie Arboléas, Mélanie Loiodice, Mélanie Kliachyna, Maria Baati, Rachid Nachon, Florian Jean, Ludovic Renard, Pierre-Yves |
| Description | Country affiliation: France Author Affiliation: Renou J ( COBRA - CNRS UMR 6014 & FR 3038, Rue Lucien Tesnière, 76821 Mont Saint Aignan, France.) |
| Abstract | Organophosphorus nerve agents (OPNAs) are highly toxic compounds that represent a threat to both military and civilian populations. They cause an irreversible inhibition of acetylcholinesterase (AChE), by the formation of a covalent P-O bond with the catalytic serine. Among the present treatment of nerve agents poisoning, pyridinium and bis-pyridinium aldoximes are used to reactivate this inhibited enzyme but these compounds do not readily cross the blood brain barrier (BBB) due to their permanent cationic charge and thus cannot efficiently reactivate cholinesterases in the central nervous system (CNS). In this study, a series of seven new uncharged oximes reactivators have been synthesized and their in vitro ability to reactivate VX and tabun-inhibited human acetylcholinesterase (hAChE) has been evaluated. The dissociation constant K(D) of inhibited enzyme-oxime complex, the reactivity rate constant kr and the second order reactivation rate constant k(r2) have been determined and have been compared to reference oximes HI-6, Obidoxime and 2-Pralidoxime (2-PAM). Regarding the reactivation of VX-inhibited hAChE, all compounds show a better reactivation potency than those of 2-PAM, nevertheless they are less efficient than obidoxime and HI-6. Moreover, one of seven described compounds presents an ability to reactivate tabun-inhibited hAChE equivalent to those of 2-PAM. |
| File Format | HTM / HTML |
| ISSN | 00092797 |
| Issue Number | 1 |
| Volume Number | 203 |
| e-ISSN | 18727786 |
| Journal | Chemico-Biological Interactions |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2013-03-25 |
| Publisher Place | Ireland |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Biochemistry Discipline Pharmacology Acetylcholinesterase Metabolism Chemical Warfare Agents Toxicity Cholinesterase Inhibitors Cholinesterase Reactivators Chemical Synthesis Pharmacology Organophosphorus Compounds Chemistry Drug Evaluation, Preclinical Electrochemistry Gpi-linked Proteins Humans Molecular Structure Obidoxime Chloride Oximes Pralidoxime Compounds Pyridinium Compounds Recombinant Proteins Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Toxicology |
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