Unsymmetric Mono- and Dinuclear Platinum(IV) Complexes Featuring an Ethylene Glycol Moiety: Synthesis, Characterization, and Biological Activity
详细信息 查看全文
- 作者：Verena Pichler ; Petra Heffeter ; Seied M. Valiahdi ; Christian R. Kowol ; Alexander Egger ; Walter Berger ; Michael A. Jakupec ; Markus Galanski ; Bernhard K. Keppler
- 刊名：Journal of Medicinal Chemistry
- 出版年：2012
- 出版时间：December 27, 2012
- 年：2012
- 卷：55
- 期：24
- 页码：11052-11061
- 全文大小：364K
- 年卷期：v.55,no.24(December 27, 2012)
- ISSN：1520-4804
文摘
Eight novel mononuclear and two dinuclear platinum(IV) complexes were synthesized and characterized by elemental analysis, one- and two-dimensional NMR spectroscopy, mass spectrometry, and reversed-phase HPLC (log聽kw) and in one case by X-ray diffraction. Cytotoxicity of the compounds was studied in three human cancer cell lines (CH1, SW480, and A549) by means of the MTT assay, featuring IC50 values to the low micromolar range. Furthermore a selected set of compounds was investigated in additional cancer cell lines (P31 and P31/cis, A2780 and A2780/cis, SW1573, 2R120, and 2R160) with regard to their resistance patterns, offering a distinctly different scheme compared to cisplatin. To gain further insights into the mode of action, drug uptake, DNA synthesis inhibition, cell cycle effects, and induction of apoptosis were determined for two characteristic substances.