{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:11:53Z","timestamp":1760487113184,"version":"build-2065373602"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,4,28]],"date-time":"2015-04-28T00:00:00Z","timestamp":1430179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001824","name":"Czech Science Foundation","doi-asserted-by":"crossref","award":["P502\/10\/0217"],"award-info":[{"award-number":["P502\/10\/0217"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Testing and Analysis"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:p>The present <jats:italic>in vitro<\/jats:italic> 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\u2010970, AAD\u20101154, and AAD\u20101336. Micro\u2010agar larval development test, MTT test of cytotoxicity, and biotransformation study coupled with Ultra high performance liquid chromatography\u2010tandem mass spectrometry (UHPLC\u2010MS\/MS) technique were used for this purpose. Larvae of two <jats:italic>Haemonchus contortus<\/jats:italic> strains (drug susceptible and multi\u2010drug resistant) and primary cultures of rat and ovine hepatocytes served as model systems. All AADs (including MOP) exhibited significant larvicidal effect in <jats:italic>H<\/jats:italic>. <jats:italic>contortus<\/jats:italic> susceptible as well as multi\u2010resistant strains, much higher than those of reference anthelmintics thiabendazole and flubendazole. AAD\u20101154 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\u20101154 and AAD\u20101336 can be considered as promising candidates for further <jats:italic>in vivo<\/jats:italic> testing. 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