Relevance of the leaving group for antitumor activity of new platinum(II) compounds containing anthracene derivatives as a carrier ligand
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- 作者：Patricia Marqué ; s-Gallego ; Simone Contaldi ; Hans den Dulk ; Magda Monari ; Jaap Brouwer ; Ulrich Jaehde ; Ganna V. Kalayda ; Jan Reedijk
- 关键词：Platinum(II) compounds ; Cytotoxic activity ; Platinum accumulation ; DNA platination ; Cisplatin-resistance ; Leaving groups
- 刊名：Journal of Inorganic Biochemistry
- 出版年：2009
- 出版时间：December 2009
- 年：2009
- 卷：103
- 期：12
- 页码：1602-1608
- 全文大小：364 K
文摘
A new anticancer-active platinum(II) compound [Pt(A9pyp)(dmso)(cbdca)], containing the E-1-(9-anthryl)-3-(2-pyridyl)-2-propenone ligand (abbreviated as A9pyp) has been synthesized by the replacement of the anionic chloride ligands in cis-[Pt(A9pyp)(dmso)Cl2] by the dianionic chelating cyclobutanedicarboxylate ligand (abbreviated as cbdca). The in vitro relevance of the leaving group of these new platinum(II) compounds has been investigated. Measurements of the time-dependent intracellular accumulation of both compounds in human ovarian carcinoma cell lines show that the leaving group affects their cellular uptake. In addition, the leaving group also influences DNA platination, and, therefore, has an effect on the biological activity against a pair of human ovarian carcinoma cell lines, i.e. sensitive and resistant to cisplatin.