The misuse of novichok agents in assassination attempts has been reported in the international media since 2018. These relatively new class of neurotoxic agents is claimed to be more toxic than the agents of the G and V series and so far, there is no report yet in literature about potential antidotes against them. To shed some light into this issue, we report here the design and synthesis of NTMGMP, a surrogate of A-242 and also the first surrogate of a novichok agent useful for experimental evaluation of antidotes. Furthermore, the efficiency of the current commercial oximes to reactivate NTMGMP-inhibited acetylcholinesterase (AChE) was evaluated. The Ellman test was used to confirm the complete inhibition of AChE, and to compare the subsequent rates of reactivation in vitro as well as to evaluate aging. In parallel, molecular docking, molecular dynamics and MM-PBSA studies were performed on a computational model of the human AChE (HssAChE)/NTMGMP complex to assess the reactivation performances of the commercial oximes in silico. Experimental and theoretical studies matched the exact hierarchy of efficiency and pointed to trimedoxime as the most promising commercial oxime for reactivation of AChE inhibited by A-242.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00204-022-03316-z | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Photocatalyzed Azidofunctionalization of Alkenes via Radical-Polar Crossover.
Angew Chem Int Ed Engl
January 2025
Laboratory of Catalysis and Organic Synthesis, Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne, CH-1015, Lausanne, Switzerland.
The azidofunctionalization of alkenes under mild conditions using commercially available starting materials and easily accessible reagents is reported based on a radical-polar crossover strategy. A broad range of alkenes, including vinyl arenes, enamides, enol ethers, vinyl sulfides, and dehydroamino esters, were regioselectively functionalized with an azide and nucleophiles such as azoles, carboxylic acids, alcohols, phosphoric acids, oximes, and phenols. The method led to a more efficient synthesis of 1,2-azidofunctionalized pharmaceutical intermediates when compared to previous approaches, resulting in both reduction of step count and increase in overall yield.
View Article and Find Full Text PDFOptimal fermentation of Shuanghuanglian and its effects on production performance of laying hens.
Front Vet Sci
October 2024
College of Life Science, Northeast Agricultural University, Harbin, China.
Background: Shuanghuanglian is a Chinese medicine composed of , , and . It has various effects, including anti-inflammatory, antibacterial, antiviral, and immunomodulatory effects. The fermented product of Shuanghuanglian can be used as an antibiotic alternative, as it has similar efficacy, which may improve the immunity, feed intake and utilization efficiency of laying hens, thus improving their production performance.
View Article and Find Full Text PDFThe possible connection between neutrophil-to-high-density lipoprotein ratio and cerebral perfusion in clinically established corticobasal syndrome: a pilot study.
Front Neurol
October 2024
Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
Introduction: Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are tauopathic atypical parkinsonisms. Given their overlap in terms of clinical manifestation, there is growing interest in the mechanisms leading to these entities.
Materials And Methods: In total, 71 patients were included in the study, 19 of whom were clinically diagnosed with CBS, 37 with PSP, and 15 with Parkinson's disease (PD).
First-in-human infection imaging with Zr-labelled leukocytes and comparison of scan quality with [Tc]Tc-HMPAO-labelled leukocytes.
Front Nucl Med
July 2024
Nuclear Medicine Research Infrastructure (NuMeRI) and Department of Nuclear Medicine, Steve Biko Academic Hospital, University of Pretoria, Pretoria, South Africa.
Article Synopsis
- Nuclear medicine infection imaging typically uses technetium-99m radiolabelled leukocytes with SPECT, but zirconium-89 offers improved sensitivity and image quality through PET technology, allowing delayed imaging for better accuracy in locating infections.
- A study explored the application of zirconium-labelled leukocytes for infection imaging in patients, comparing results from PET and SPECT to assess the quality and distribution of these radiolabelled cells.
- Results showed successful labelling with high efficiency and viability of the zirconium-labelled leukocytes, indicating potential benefits over traditional imaging methods.
Novel multitarget analgesic candidate SZV-1287 demonstrates potential disease-modifying effects in the monoiodoacetate-induced osteoarthritis mouse model.
Front Pharmacol
September 2024
Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, Hungary.
Introduction: Monoiodoacetate (MIA)-induced osteoarthritis (OA) is the most commonly used rodent model for testing anti-OA drug candidates. Herein, we investigated the effects of our patented multitarget drug candidate SZV-1287 (3-(4,5-diphenyl-1,3-oxazol-2-yl) propanal oxime) that is currently under clinical development for neuropathic pain and characterized the mouse model through complex functional, imaging, and morphological techniques.
Methods: Knee OA was induced by intraarticular MIA injection (0.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!