Roscovitine-based CDK inhibitors acting as N-donor ligands in the platinum(II) oxalato complexes: preparation, characterization and in vitro cytotoxicity
Language English Country France Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
20692737
DOI
10.1016/j.ejmech.2010.07.025
PII: S0223-5234(10)00505-2
Knihovny.cz E-resources
- MeSH
- Cell Line MeSH
- Cyclin-Dependent Kinases antagonists & inhibitors metabolism MeSH
- Hepatocytes drug effects MeSH
- Protein Kinase Inhibitors chemistry pharmacology MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Neoplasms drug therapy enzymology MeSH
- Organoplatinum Compounds chemistry pharmacology MeSH
- Oxalates chemistry pharmacology MeSH
- Antineoplastic Agents chemistry pharmacology MeSH
- Purines chemistry pharmacology MeSH
- Roscovitine MeSH
- Spectrum Analysis MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cyclin-Dependent Kinases MeSH
- Protein Kinase Inhibitors MeSH
- Organoplatinum Compounds MeSH
- Oxalates MeSH
- Antineoplastic Agents MeSH
- Purines MeSH
- Roscovitine MeSH
The reactions of potassium bis(oxalato)platinate dihydrate with two molar equivalents of the potent adenine-based cyclin-dependent kinase inhibitor 2-(1-ethyl-2-hydroxyethylamino)-N6-(benzyl)-9-isopropyladenine (Roscovitine; Ros) and its benzyl-substituted analogues, i.e. 2-(1-ethyl-2-hydroxyethylamino)-N6-(2-methoxybenzyl)-9-isopropyladenine (2OMeRos), 2-(1-ethyl-2-hydroxyethylamino)-N6-(3-methoxybenzyl)-9-isopropyladenine (3OMeRos) and 2-(1-ethyl-2-hydroxyethylamino)-N6-(4-methoxybenzyl)-9-isopropyladenine (4OMeRos), were performed and the [Pt(ox)(Ros)(2)].(3/4)H(2)O (1), [Pt(ox)(2OMeRos)(2)].H(2)O (2), [Pt(ox)(3OMeRos)(2)].(1/2)H(2)O (3) and [Pt(ox)(4OMeRos)(2)].(3/4)H(2)O (4) platinum(II) oxalato complexes were obtained. The methods of the elemental analysis, IR, Raman and NMR spectroscopy, ESI + mass spectrometry, molar conductivity measurement and TG/DTA thermal analysis were performed to characterize the obtained products. The complexes 1-4 involve tetracoordinated central Pt(II) atom with one bidentate-coordinated oxalate dianion (ox) and two monodentate adenine-based molecules (nRos), thus giving the square-planar geometry around the metal centre with a PtN(2)O(2) donor set. In vitro cytotoxic activity of the complexes against ovarian carcinoma (A2780), cisplatin resistant ovarian carcinoma (A2780cis), malignant melanoma (G-361), lung carcinoma (A549), cervix epitheloid carcinoma (HeLa), breast adenocarcinoma (MCF7) and osteosarcoma (HOS) human cancer cell lines was evaluated. All the tested complexes exceeded the in vitro cytotoxicity of cisplatin and oxaliplatin against HeLa, A2780cis and, except for 2, also against HOS cancer cells. The complex 1 was also tested for its cytotoxicity in primary cultures of human hepatocytes and it was not found to be hepatotoxic up to the concentration of 50.0 microM.
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