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Polyalkoxybenzenes from Plants. 5. Parsley Seed Extract in Synthesis of Azapodophyllotoxins Featuring Strong Tubulin Destabilizing Activity in the Sea Urchin Embryo and Cell Culture Assaysстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Scopus,
Web of Science
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 18 июля 2013 г.
- Авторы: Semenova Marina N., Kiselyov Alex S., Tsyganov Dmitry V., Konyushkin Leonid D., Firgang Sergei I., Semenov Roman V., Malyshey Oleg R., Raihstat Mikhail M., Fuchs Fabian, Stielow Anne, Lantow Margareta, Philchenkov Alex A., Zavelevich Michael P., Zefirov NIkolay S., Kuznetsov Sergei A.
- Журнал: Journal of Medicinal Chemistry
- Том: 54
- Номер: 20
- Год издания: 2011
- Издательство: American Chemical Society
- Местоположение издательства: United States
- Первая страница: 7138
- Последняя страница: 7149
- DOI: 10.1021/jm200737s
- Аннотация: A series of 4-azapodophyllotoxin derivatives with modified rings B and E have been synthesized using allylpolyalkoxybenzenes from parsley seed oil. The targeted molecules were evaluated in vivo in a phenotypic sea urchin embryo assay for antimitotic and tubulin destabilizing activity. The most active compounds identified by the in vivo sea urchin embryo assay featured myristicin-derived ring E (4e, 6e, and 8e). These molecules were determined to be more potent than podophyllotoxin. Cytotoxic effects of selected molecules were further confirmed and evaluated by conventional assays with A549 and Jurkat human leukemic T-cell lines including cell growth inhibition, cell cycle arrest, cellular microtubule disruption, and induction of apoptosis. The ring B modification yielded 6-OMe substituted molecule 8e as the most active compound. Finally, in Jurkat cells, compound 8e induced caspase-dependent apoptosis mediated by the apical caspases-2 and -9 and not caspase-8, implying the involvement of the intrinsic caspase-9-dependent apoptotic pathway.
- Добавил в систему: Зефиров Николай Серафимович