Cytotoxicity of acetylcholinesterase reactivators evaluated in vitro and its relation to their structure
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F19%3A00534991" target="_blank" >RIV/60162694:G44__/19:00534991 - isvavai.cz</a>
Alternative codes found
RIV/00179906:_____/19:10393078
Result on the web
<a href="http://www.tandfonline.com/doi/full/10.1080/01480545.2018.1432641" target="_blank" >http://www.tandfonline.com/doi/full/10.1080/01480545.2018.1432641</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1080/01480545.2018.1432641" target="_blank" >10.1080/01480545.2018.1432641</a>
Alternative languages
Result language
angličtina
Original language name
Cytotoxicity of acetylcholinesterase reactivators evaluated in vitro and its relation to their structure
Original language description
The development of acetylcholinesterase reactivators, i.e., antidotes against organophosphorus poisoning, is an important goal of defense research. The aim of this study was to compare cytotoxicity and chemical structure of five currently available oximes (pralidoxime, trimedoxime, obidoxime, methoxime, and asoxime) together with four perspective oximes from K-series (K027, K074, K075, and K203). The cytotoxicity of tested substances was measured using two methods - colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay and impedance based real-time cytotoxicity assay - in three different cell lines (HepG2, ACHN, and NHLF). Toxicity was subsequently expressed as toxicological index IC50. The tested compounds showed different cytotoxicity ranging from 0.92 to 40.06mM. In HepG2 cells, K027 was the least and asoxime was the most toxic reactivator. In ACHN and NHLF cell lines, trimedoxime was the compound with the lowest adverse effects, whereas the highest toxicity was found in methoxime-treated cells. The results show that at least five structural features affect the reactivators' toxicity such as the number of oxime groups in the molecule, their position on pyridinium ring, the length of carbon linker, and the oxygen substitution or insertion of the double bond into the connection chain. Newly synthetized oximes with IC50 ≥ 1mM evaluated in this three cell lines model might appear suitable for further testing.
Czech name
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Czech description
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Classification
Type
J<sub>SC</sub> - Article in a specialist periodical, which is included in the SCOPUS database
CEP classification
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OECD FORD branch
30108 - Toxicology
Result continuities
Project
—
Continuities
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Drug and Chemical Toxicology
ISSN
0148-0545
e-ISSN
1525-6014
Volume of the periodical
42
Issue of the periodical within the volume
3
Country of publishing house
GB - UNITED KINGDOM
Number of pages
5
Pages from-to
252-256
UT code for WoS article
000460641800003
EID of the result in the Scopus database
2-s2.0-85041827367