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Synthesis and SAR requirements of adamantane-colchicine conjugates with both microtubule depolymerizing and tubulin clustering activitiesстатья
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: 18 июля 2013 г.
- Авторы: Zefirova Olga N., Nurieva Evgeniya V., Shishov Dmitrii V., Baskin Igor I., Fuchs Fabian, Lemcke Heiko, Schroeder Fabian, Weiss Dieter G., Zefirov Nikolay S., Kuznetsov Sergei A.
- Журнал: Bioorganic and Medicinal Chemistry
- Том: 19
- Номер: 18
- Год издания: 2011
- Издательство: Pergamon Press Ltd.
- Местоположение издательства: United Kingdom
- Первая страница: 5529
- Последняя страница: 5538
- DOI: 10.1016/j.bmc.2011.07.040
- Аннотация: A series of analogues of conjugate 1, combining an adamantane-based paclitaxel (taxol) mimetic with colchicine was synthesized and tested for cytotoxicity in a cell-based assay with the human lung carcinoma cell line A549. The most active compounds (10 EC(50) 2 +/- 1.0 nM, 23 EC(50) 6 +/- 1.4 nM, 26 EC(50) 5 +/- 1.8 nM, 28 EC(50) 11 +/- 1.7 nM, 30 EC(50) 4.8 +/- 0.5 nM) were found to interfere with the microtubule dynamics in an interesting manner. Treatment of the cells with these compounds promoted disassembly of microtubules followed by the formation of stable tubulin clusters. Structure-activity relationships for the analogues of 23 revealed the sensitivity of both cytotoxicity and tubulin clustering ability to the linker length. The presence of adamantane (or another bulky hydrophobic and non-aromatic moiety) in 23 was found to play an important role in the formation of tubulin clusters. Structural requirements for optimal activity have been partially explained by molecular modeling. (C) 2011 Elsevier Ltd. All rights reserved.
- Добавил в систему: Зефиров Николай Серафимович