Comparison of biotransformation and efficacy of aminoacetonitrile anthelmintics in vitro
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F16%3A10328430" target="_blank" >RIV/00216208:11160/16:10328430 - isvavai.cz</a>
Alternative codes found
RIV/00216275:25310/16:39901798
Result on the web
<a href="http://onlinelibrary.wiley.com/doi/10.1002/dta.1806/full" target="_blank" >http://onlinelibrary.wiley.com/doi/10.1002/dta.1806/full</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/dta.1806" target="_blank" >10.1002/dta.1806</a>
Alternative languages
Result language
angličtina
Original language name
Comparison of biotransformation and efficacy of aminoacetonitrile anthelmintics in vitro
Original language description
The present in vitro study was designed to test and compare anthelmintic activity, hepatotoxicity, and biotransformation of four selected aminoacetonitrile derivatives (AADs): monepantel (MOP, anthelmintic approved for the treatment), AAD-970, AAD-1154, and AAD-1336. Micro-agar larval development test, MTT test of cytotoxicity, and biotransformation study coupled with Ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technique were used for this purpose. Larvae of two Haemonchus contortus strains (drug susceptible and multi-drug resistant) and primary cultures of rat and ovine hepatocytes served as model systems. All AADs (including MOP) exhibited significant larvicidal effect in H. contortus susceptible as well as multi-resistant strains, much higher than those of reference anthelmintics thiabendazole and flubendazole. AAD-1154 provides the best results for most tested parameters among all AADs in this study. The cytotoxicity test showed that all AADs can be considered as nontoxic for hepatocytes. In the biotransformation study, Phase I and Phase II metabolites of AADs were identified and schemes of possible metabolic pathways in ovine hepatocytes were proposed. Biotransformation of MOP was much more extensive than biotransformation of other AADs. Based on obtained results, AAD-1154 and AAD-1336 can be considered as promising candidates for further in vivo testing.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
GJ - Diseases and animal vermin, veterinary medicine
OECD FORD branch
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Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Drug Testing and Analysis
ISSN
1942-7603
e-ISSN
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Volume of the periodical
8
Issue of the periodical within the volume
2
Country of publishing house
GB - UNITED KINGDOM
Number of pages
7
Pages from-to
214-220
UT code for WoS article
000370199000008
EID of the result in the Scopus database
2-s2.0-84958752673