Elimination kinetics and molecular reaction mechanisms of cyclosarin (GF) by an oxime substituted β-cyclodextrin derivative in vitro

Organophosphorus agents (OPs) irreversibly inhibit acetylcholinesterase (AChE) causing a major cholinergic syndrome. The medical counter-measures of OP poisoning have not evolved for the last 30 years with carbamates for pretreatment, pyridinium oximes-based AChE reactivators, antimuscarinic drugs and neuroprotective benzodiazepines for postexposure treatment. These drugs ensure protection of peripheral nervous system and mitigate acute effects of OP lethal doses. However, they have significant limitations. Pyridostigmine and oximes do not protect/reactivate central AChE. Oximes poorly reactivate AChE inhibited by phosphoramidates. In addition, current neuroprotectants do not protect the central nervous system shortly after the onset of seizures when brain damage becomes irreversible. New therapeutic approaches for pre-and post-exposure treatments involve detoxification of OP molecules before they reach their molecular targets by administrating catalytic bioscavengers, among them phosphotriesterases are the most promising. Novel generation of broad spectrum reactivators are designed for crossing the blood-brain barrier and reactivate central AChE.

show abstract

“…The study of their mechanism indicates that they belong to the stoichiometric scavenger family (Kranawetvogl et al . ; Bierwisch et al . ).…”

Section: Pretreatmentmentioning

confidence: 99%

Cholinesterase reactivators and bioscavengers for pre‐ and post‐exposure treatments of organophosphorus poisoning

Masson

Nachon²

2017

Journal of Neurochemistry

122

105

View full text Add to dashboard Cite

show abstract

“…(100 mg/kg) 5 min prior to cyclosarin s.c. For them, the systemic signs of poisoning almost completely disappeared. Reiter et al investigated the detoxification mechanism of 20b and demonstrated a stereoselective hydrolysis of the most toxic (−)-cyclosarin [ 79 ]. As previously described, the formation of an intermediate inclusion complex is likely to occurred.…”

Section: Reviewmentioning

confidence: 99%

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

Letort¹,

Balieu²,

Erb³

et al. 2016

Beilstein J. Org. Chem.

View full text Add to dashboard Cite

SummaryThe aim of this review is to provide an update on the current use of cyclodextrins against organophosphorus compound intoxications. Organophosphorus pesticides and nerve agents play a determinant role in the inhibition of cholinesterases. The cyclic structure of cyclodextrins and their toroidal shape are perfectly suitable to design new chemical scavengers able to trap and hydrolyze the organophosphorus compounds before they reach their biological target.

show abstract

“…Furthermore, functionalised-CDs have been proposed for use in CWA decontamination and medical countermeasures, particularly with regard to cyclosarin (GF). 19,20 A recent review by Estour et al summarises work in the interactions of both OP nerve agents and other toxic OP compounds, such as pesticides, with CDs. 21 Studies of the complexes formed between OP CWAs and CDs by NMR methods and appropriate comparison to the inclusion behaviour of simulants has not, to the best of our knowledge, been widely investigated.…”

Section: Introductionmentioning

confidence: 99%

Experimental and computational study of the inclusion complexes of β-cyclodextrin with the chemical warfare agent soman (GD) and commonly used simulants

et al. 2017

View full text Add to dashboard Cite

show abstract

Elimination kinetics and molecular reaction mechanisms of cyclosarin (GF) by an oxime substituted β-cyclodextrin derivative in vitro

Cited by 13 publications

References 28 publications

Cholinesterase reactivators and bioscavengers for pre‐ and post‐exposure treatments of organophosphorus poisoning

Cholinesterase reactivators and bioscavengers for pre‐ and post‐exposure treatments of organophosphorus poisoning

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

Experimental and computational study of the inclusion complexes of β-cyclodextrin with the chemical warfare agent soman (GD) and commonly used simulants

Contact Info

Product

Resources

About