Background: Based on in vitro and in vivo rat experiments, the newly developed acetylcholinesterase (AChE) reactivator, K203, appears to be much more effective in the treatment of tabun poisonings than currently fielded oximes.
Methods: To determine if this reactivating efficacy would extend to humans, studies were conducted in vitro using human brain homogenate as the source of AChE. The efficacy of K203 was compared with commercially available oximes; pralidoxime, obidoxime and asoxime (HI-6).
Results: Reactivation studies showed that K203 was the most effective reactivator with a second order kinetic constant (k) of 2142 min. M, which was 51 times higher than that obtained for obidoxime (k = 42 min. M). Both pralidoxime and asoxime (HI-6) failed to significantly reactivate tabun-inhibited human AChE.
Discussion: According to these results and previous studies, using K203, it appears that oxime K203 is the most effective reactivator of tabun-inhibited cholinesterase in several species including humans and should be considered as a possible medical countermeasure to tabun exposure.
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http://dx.doi.org/10.1186/s40360-018-0196-3 | DOI Listing |
Bioorg Chem
December 2024
University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, 500 03 Hradec Kralove, Czech Republic; University Hospital in Hradec Kralove, Biomedical Research Centre, Sokolska 581, 500 05 Hradec Kralove, Czech Republic. Electronic address:
Mono-quaternary pyridinium oximes derived from K-oximes K027, K048 and K203 were designed, synthesized and evaluated for the reactivation of organophosphate-inhibited cholinesterases. The incorporation of the halogen atoms to the structure decreased the pK value of the oxime group resulting in an increased formation of oximate necessary for reactivation. The stability and pK values were found to be similar to analogous bis-quaternary compounds.
View Article and Find Full Text PDFChem Res Toxicol
December 2023
Department of Analytical Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, Hradec Králové 500 05, Czechia.
Oxime reactivators of acetylcholinesterase (AChE) are used as causal antidotes for intended and unintended poisoning by organophosphate nerve agents and pesticides. Despite all efforts to develop new AChE reactivators, none of these drug candidates replaced conventional clinically used oximes. In addition to the therapeutic efficacy, determining the safety profile is crucial in preclinical drug evaluation.
View Article and Find Full Text PDFFront Immunol
November 2023
Department of Chemistry, Kookmin University, Seoul, Republic of Korea.
Introduction: The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has caused unprecedented health and socioeconomic crises, necessitating the immediate development of highly effective neutralizing antibodies. Despite recent advancements in anti-SARS-CoV-2 receptor-binding domain (RBD)-specific monoclonal antibodies (mAbs) derived from convalescent patient samples, their efficacy against emerging variants has been limited. In this study, we present a novel dual-targeting strategy using bispecific antibodies (bsAbs) that specifically recognize both the SARS-CoV-2 RBD and fusion peptide (FP), crucial domains for viral attachment to the host cell membrane and fusion in SARS-CoV-2 infection.
View Article and Find Full Text PDFFood Chem Toxicol
September 2022
Biomedical Research Center, University Hospital, Hradec Kralove, Czech Republic; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic. Electronic address:
Oxime reactivators are causal antidotes for organophosphate intoxication. Herein, the toxicity, pharmacokinetics, and reactivation effectiveness of o-chlorinated bispyridinium oxime K870 are reported. Oxime K870 was found to have a safe profile at a dose of 30 mg/kg in rats.
View Article and Find Full Text PDFMicroorganisms
February 2022
Division of Agricultural Microbiology, National Institute of Agricultural Sciences, Rural Development Administration, Wanju 55365, Korea.
Tomatoes are cultivated worldwide, and are economically important. subsp. () is a pathogen that causes canker and wilting in tomatoes, resulting in serious damage to tomato plants.
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