Nejvíce citovaný článek - PubMed ID 35666269
Are the current commercially available oximes capable of reactivating acetylcholinesterase inhibited by the nerve agents of the A-series?
The risk of the use of toxic chemicals for unlawful acts has been a matter of concern for different governments and multilateral agencies. The Organisation for the Prohibition of Chemical Weapons (OPCW), which oversees the implementation of the Chemical Weapons Convention (CWC), considering recent events employing chemical warfare agents as means of assassination, has recently included in the CWC "Annex on Chemicals" some organophosphorus compounds that are regarded as acting in a similar fashion to the classical G- and V-series of nerve agents, inhibiting the pivotal enzyme acetylcholinesterase. Therefore, knowledge of the activity of the pyridinium oximes, the sole class of clinically available acetylcholinesterase reactivators to date, is plainly justified. In this paper, continuing our research efforts in medicinal chemistry on this class of toxic chemicals, we synthesized an A-230 nerve agent surrogate and applied a modified Ellman's assay to evaluate its ability to inhibit our enzymatic model, acetylcholinesterase from Electrophorus eel, and if the clinically available antidotes are able to rescue the enzyme activity for the purpose of relating the findings to the previously disclosed in silico data for the authentic nerve agent and other studies with similar A-series surrogates. Our experimental data indicates that pralidoxime is the most efficient compound for reactivating acetylcholinesterase inhibited by A-230 surrogate, which is the opposite of the in silico data previously disclosed.
- Klíčová slova
- A-230, Acetylcholinesterase, Antidotes, Chemical Weapons Convention, Nerve agent surrogates,
- MeSH
- acetylcholinesterasa * metabolismus MeSH
- antidota farmakologie MeSH
- chemické bojové látky * toxicita MeSH
- cholinesterasové inhibitory * toxicita MeSH
- nervová bojová látka * toxicita MeSH
- organothiofosforové sloučeniny toxicita MeSH
- oximy * farmakologie MeSH
- pralidoximové sloučeniny farmakologie MeSH
- pyridinové sloučeniny * farmakologie MeSH
- reaktivátory cholinesterasy * farmakologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- acetylcholinesterasa * MeSH
- antidota MeSH
- chemické bojové látky * MeSH
- cholinesterasové inhibitory * MeSH
- nervová bojová látka * MeSH
- organothiofosforové sloučeniny MeSH
- oximy * MeSH
- pralidoxime MeSH Prohlížeč
- pralidoximové sloučeniny MeSH
- pyridinové sloučeniny * MeSH
- reaktivátory cholinesterasy * MeSH
"Novichok" refers to a new group of nerve agents called the A-series agents. Their existence came to light in 2018 after incidents in the UK and again in 2020 in Russia. They are unique organophosphorus-based compounds developed during the Cold War in a program called Foliant in the USSR. This review is based on original chemical entities from Mirzayanov's memoirs published in 2008. Due to classified research, a considerable debate arose about their structures, and hence, various structural moieties were speculated. For this reason, the scientific literature is highly incomplete and, in some cases, contradictory. This review critically assesses the information published to date on this class of compounds. The scope of this work is to summarize all the available and relevant information, including the physicochemical properties, chemical synthesis, mechanism of action, toxicity, pharmacokinetics, and medical countermeasures used to date. The environmental stability of A-series agents, the lack of environmentally safe decontamination, their high toxicity, and the scarcity of information on post-contamination treatment pose a challenge for managing possible incidents.
- Klíčová slova
- A-series agents, Analysis, Environmental stability, Physicochemical properties, Therapy, Toxicity,
- MeSH
- kontaminace léku * MeSH
- nervová bojová látka * toxicita MeSH
- organofosforové sloučeniny MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- nervová bojová látka * MeSH
- organofosforové sloučeniny MeSH