In vitro comparison of the acetylcholinesterase inhibition caused by V- and A-series nerve agents' surrogates

Article Toxicology

Application of toxicology in silico methods for prediction of acute toxicity (LD50) for Novichoks

Maciej Noga et al.

Summary: Novichoks, the fourth generation chemical warfare agents produced by the Soviet Union during the Cold War, have paralytic and convulsive effects. The public debate about their true nature highlights the importance of examining their properties, especially the toxicological aspects.

ARCHIVES OF TOXICOLOGY (2023)

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Article Nanoscience & Nanotechnology

Effective Degradation of Novichok Nerve Agents by the Zirconium Metal-Organic Framework MOF-808

Martijn C. de Koning et al.

Summary: MOF-808 has been found to be a highly efficient and regenerable catalyst for the hydrolysis of Novichok agents. The degradation of Novichoks proceeds in two consecutive hydrolysis steps, with an intermediate acting as a competitive substrate. Under acidic conditions, a moderately toxic intermediate is formed, which can be efficiently hydrolyzed by MOF-808 under basic conditions.

ACS APPLIED MATERIALS & INTERFACES (2022)

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Article Biochemical Research Methods

Unambiguous identification and determination of A234-Novichok nerve agent biomarkers in biological fluids using GC-MS/MS and LC-MS/MS

Fatemeh Mirbabaei et al.

Summary: The present study developed suitable methods for identifying and determining biomarkers of A234-Novichok in urine and plasma samples. Multiple biomarkers were investigated using sensitive techniques, and the developed methods may be used for verification purposes and proficiency tests in the field of chemical weapons.

ANALYTICAL AND BIOANALYTICAL CHEMISTRY (2022)

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Article Chemistry, Analytical

Nontargeted High-Resolution Mass Spectrometric Workflow for the Detection of Butyrylcholinesterase-Derived Adducts with Organophosphorus Toxicants and Structural Characterization of Their Phosphyl Moiety after In-Source Fragmentation

Harald John et al.

Summary: Organophosphorus (OP) nerve agents have been widely used for chemical warfare, assassination, and murder. Forensic methods are needed to identify known and unknown OP poisons. This study presents a non-targeted mass spectrometry-based workflow using a high-resolution Orbitrap mass spectrometer to detect unknown agents. BChE adducts are extracted and proteolyzed to obtain a phosphylated nonapeptide (NP) biomarker. This workflow can effectively detect adducts of various OP poisons, including unknown agents.

ANALYTICAL CHEMISTRY (2022)

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Article Food Science & Technology

Theoretical assessment of the performances of commercial oximes on the reactivation of acetylcholinesterase inhibited by the nerve agent A-242 (novichok)

Marcelo C. Santos et al.

Summary: This study assessed the performances of four commercial oximes when in contact with HssAChE inhibited by the nerve agent A-242. The results suggest limited efficacy of the commercial oximes in reactivating the enzyme, with trimedoxime showing the most promising potential.

FOOD AND CHEMICAL TOXICOLOGY (2022)

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Article Pharmacology & Pharmacy

Pharmacokinetics of three novel pyridinium aldoxime acetylcholinesterase reactivators in female rats

Brian S. Backer et al.

Summary: A novel lipophilic substituted phenoxyalkyl pyridinium oxime platform has been developed to reactivate acetylcholinesterase inhibited by organophosphates. The lead compound, Oxime 20, has shown superior efficacy in rats compared to the standard treatment, 2-PAM, in terms of survival and neuroprotection against lethal doses of nerve agent surrogates. The pharmacokinetic data suggests that Oxime 20 has potential as a superior therapeutic for nerve agent poisoning.

TOXICOLOGY AND APPLIED PHARMACOLOGY (2022)

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Article Biochemical Research Methods

Simulation of the electron ionization mass spectra of the Novichok nerve agent

Francisco C. S. Chernicharo et al.

Summary: Novichok is a feared and controversial nerve agent that has been of concern in recent years. Its existence was only confirmed after the Salisbury attack in 2018, and it was subsequently included in the list of the most dangerous chemicals of the Chemical Weapons Convention. However, information related to its electron ionization mass spectrometry (EI/MS) is still scarce, making investigations into Novichok urgent.

JOURNAL OF MASS SPECTROMETRY (2021)

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Article Chemistry, Physical

Electronic and spectroscopic properties of A-series nerve agents

Leandro A. Vieira et al.

Summary: This study used Density Functional Theory to compute molecular, spectroscopic, and electronic properties of A-series nerve agents, finding that these agents have similar reactivities but are less reactive than VX and VR nerve agents. Results suggest that A-series molecules have two electropositive centers and exhibit high lipophilic character.

COMPUTATIONAL AND THEORETICAL CHEMISTRY (2021)

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Article Biochemistry & Molecular Biology

Design, synthesis, in silico studies and in vitro evaluation of isatin-pyridine oximes hybrids as novel acetylcholinesterase reactivators

Daniel A. S. Kitagawa et al.

Summary: Novel isatin derivatives linked to a pyridinium 4-oxime moiety by an alkyl chain with improved calculated properties showed comparable in vitro reactivation against paraoxon- and NEMP-inhibited acetylcholinesterase, indicating their potential as promising compounds for tackling organophosphorus poisoning.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2021)

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Review Biochemistry & Molecular Biology