Back to Search
Start Over
SAR study to find optimal cholinesterase reactivator against organophosphorous nerve agents and pesticides
- Source :
- Archives of Toxicology. 90:2831-2859
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Irreversible inhibition of acetylcholinesterase (AChE) by organophosphates leads to many failures in living organism and ultimately in death. Organophosphorus compounds developed as nerve agents such as tabun, sarin, soman, VX and others belong to the most toxic chemical warfare agents and are one of the biggest threats to the modern civilization. Moreover, misuse of nerve agents together with organophosphorus pesticides (e.g. malathion, paraoxon, chlorpyrifos, etc.) which are annually implicated in millions of intoxications and hundreds of thousand deaths reminds us of insufficient protection against these compounds. Basic treatments for these intoxications are based on immediate administration of atropine and acetylcholinesterase reactivators which are currently represented by mono- or bis-pyridinium aldoximes. However, these antidotes are not sufficient to ensure 100 % treatment efficacy even they are administered immediately after intoxication, and in general, they possess several drawbacks. Herein, we have reviewed new efforts leading to the development of novel reactivators and proposition of new promising strategies to design novel and effective antidotes. Structure-activity relationships and biological activities of recently proposed acetylcholinesterase reactivators are discussed and summarized. Among further modifications of known oximes, the main attention has been paid to dual binding site ligands of AChE as the current mainstream strategy. We have also discussed new chemical entities as potential replacement of oxime functional group.
- Subjects :
- 0301 basic medicine
Cholinesterase Reactivators
Sarin
Protein Conformation
Health, Toxicology and Mutagenesis
Antidotes
Molecular Conformation
Pyridinium Compounds
Pharmacology
Ligands
Toxicology
Structure-Activity Relationship
03 medical and health sciences
chemistry.chemical_compound
Organophosphate Poisoning
Organophosphorus Compounds
0302 clinical medicine
Catalytic Domain
Soman
medicine
Animals
Humans
Pesticides
Nerve agent
Tabun
Binding Sites
Molecular Structure
Paraoxon
Chemistry
Organophosphate
General Medicine
Acetylcholinesterase
030104 developmental biology
Drug Design
030220 oncology & carcinogenesis
Chlorpyrifos
Cholinesterase Inhibitors
Nerve Agents
medicine.drug
Subjects
Details
- ISSN :
- 14320738 and 03405761
- Volume :
- 90
- Database :
- OpenAIRE
- Journal :
- Archives of Toxicology
- Accession number :
- edsair.doi.dedup.....282585af28ac1329336b3fe267272cf0