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(1 R,2 R,4 R)-4-Methyl-1,2-cyclohexanediamineoxalatoplatinum(II): A Novel Enantiomerically Pure Oxaliplatin Derivative Showing Improved Anticancer Activity in Vivoстатья
Статья опубликована в высокорейтинговом журнале
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: Abramkin S.A., Jungwirth U., Valiahdi S.M., Dworak C., Habala L., Meelich K., Berger W., Jakupec M.A., Hartinger C.G., Nazarov A.A., Galanski M., Keppler B.K.
- Журнал: Journal of Medicinal Chemistry
- Том: 53
- Номер: 20
- Год издания: 2010
- Издательство: American Chemical Society
- Местоположение издательства: United States
- Первая страница: 7356
- Последняя страница: 7364
- DOI: 10.1021/jm100953c
- Аннотация: Novel derivatives of the clinically established anticancer drug oxaliplatin were synthesized. Cytotoxicity of the compounds was studied in six human cancer cell lines by means of the MTT assay. Additionally, most promising complexes were also investigated in cisplatin- and oxaliplatin-resistant human cancer cell models. The therapeutic efficacy in vivo was studied in the murine L1210 leukemia model. Most remarkably, (1R,2R,4R)-4-methyl-1,2-cyclohexanediamine oxalatoplatinum(II), comprising an equatorial methyl substituent at position 4 of the cyclohexane ring, was as potent as oxaliplatin in vitro but distinctly more effective in the L1210 model in vivo at the optimal dose. The advantage observed in the in vivo situation was mainly based on a more favorable therapeutic index. The maximum tolerated dose of the novel analogue was higher than that of oxaliplatin and caused a greater increase in life span (>200% versus 152%), with more animals experiencing long-term survival (5/6 versus 2/6). These data support further (pre)clinical development of the methyl-substituted oxaliplatin analogue with improved anticancer activity. © 2010 American Chemical Society.
- Добавил в систему: Назаров Алексей Анатольевич