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Synthesis and biological testing of (5Z)-2-aryl-5-arylmethylidene-3,5-dihydro-4H-imidazol-4-ones as antimitotic agentsстатья
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 26 сентября 2016 г.
- Авторы: Beloglazkina Anastasia A., Birgit Wobith, Barskaia Elena S., Zefirov Nikolay A., Majouga Alexander G., Beloglazkina Elena K., Zyk Nikolay V., Kuznetsov Sergei A., Zefirova Olga N.
- Журнал: Medicinal Chemistry Research
- Том: 25
- Номер: 6
- Год издания: 2016
- Издательство: Birkhaeuser
- Местоположение издательства: United States
- Первая страница: 1239
- Последняя страница: 1249
- DOI: 10.1007/s00044-016-1566-2
- Аннотация: Compounds interacting with cell protein tubulin and microtubules represent an important type of antimitotic agents. A series of tubulin-targeted 2-aryl-4-benzoyl-imidazoles were reported to possess high cytotoxicity, and so, we prepared a series of structural isomers of these to be evaluated as antimitotic agents. The synthesis of the novel (Z)-2-aryl-5-arylmethylidene-3,5-dihydro-4H-imidazol-4-ones involved coupling of substituted hippuric acids with aromatic aldehydes. Subsequent conversion of the resulting oxazolones to the corresponding imidazolones was carried out under microwave irradiation in the presence of urea and ammonium acetate. The cytotoxicity of the majority of the compounds to human epithelial carcinoma cancer cell line A549 was in the sub-micromolar range and was found to be more sensitive to the substituents on the 5-arylmethylidene fragment than on the 2-aryl ring in general. The cytotoxicities of the synthesized compounds were lower than those of the previously reported isomeric 2-aryl-4-benzoyl-imidazoles, and the basic structure–activity relationships in the isomeric pairs were different. Synthesized (5Z)-5-[(4-bromophenyl)methylidene]-2-(4-methylphenyl)-3,5-dihydro-4H-imidazol-4-one, which had the highest cytotoxicity (IC50 ~ 440 nM) in the series of novel compounds, had a definite cytostatic effect on the A549 cells, but its antiproliferative properties were not linked to action on the microtubules. This would be an interesting lead compound for additional investigation into the mechanism of cytostatic action, and further structural optimization.
- Добавил в систему: Белоглазкина Елена Кимовна