Recent events involving nerve agents of the A-Series, a once elusive class of chemical warfare agents, have provoked a great concern in the international community. In this paper, continuing our research efforts in Medicinal Chemistry at the Brazilian Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN) (an OPCW-designated Laboratory for environmental samples), we explore ANMP, an A-230 surrogate, in the search for new treatment options for intoxications caused by these chemicals. Five isatin-pyridine oxime hybrids were evaluated as acetylcholinesterase (AChE) reactivators using a modified Ellman's assay. Our results indicate that monocationic hybrids with five methylene units, as well as its oxa-analog, are promising compounds for the design of new AChE reactivators.

• Klíčová slova
• Acetylcholinesterase, Antidotes, Chemical Weapons Convention, Isatin hybrids, Nerve agents,
• MeSH
• acetylcholinesterasa metabolismus   MeSH
• chemické bojové látky * toxicita   chemie   MeSH
• cholinesterasové inhibitory * toxicita   chemie   MeSH
• isatin * chemie   farmakologie   analogy a deriváty   MeSH
• oximy * chemie   farmakologie   MeSH
• počítačová simulace MeSH
• pyridiny * chemie   farmakologie   MeSH
• reaktivátory cholinesterasy * farmakologie   chemie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• chemické bojové látky * MeSH
• cholinesterasové inhibitory * MeSH
• isatin * MeSH
• oximy * MeSH
• pyridiny * MeSH
• reaktivátory cholinesterasy * MeSH

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