Platinum(II) carboxylato complexes containing 7-azaindoles as N-donor carrier ligands showed cytotoxicity against cancer cell lines
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
27350081
DOI
10.1016/j.jinorgbio.2016.06.018
PII: S0162-0134(16)30181-7
Knihovny.cz E-resources
- Keywords
- 7-Azaindole derivatives, Antitumour activity, Cell cycle, Decanoato, Malonato, Platinum(II) complexes,
- MeSH
- Cell Line MeSH
- Drug Resistance, Neoplasm drug effects MeSH
- Cisplatin chemistry MeSH
- Epithelial Cells drug effects pathology MeSH
- Fibroblasts cytology drug effects MeSH
- Glutathione chemistry MeSH
- Indoles chemistry MeSH
- Inhibitory Concentration 50 MeSH
- Coordination Complexes chemical synthesis pharmacology MeSH
- G1 Phase Cell Cycle Checkpoints drug effects MeSH
- Guanosine Monophosphate chemistry MeSH
- Carboxylic Acids chemistry MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Organoplatinum Compounds chemical synthesis pharmacology MeSH
- Antineoplastic Agents chemical synthesis pharmacology MeSH
- Cell Survival drug effects MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 7-azaindole dimer MeSH Browser
- Cisplatin MeSH
- Glutathione MeSH
- Indoles MeSH
- Coordination Complexes MeSH
- Guanosine Monophosphate MeSH
- Carboxylic Acids MeSH
- Organoplatinum Compounds MeSH
- Antineoplastic Agents MeSH
The platinum(II) malonato (Mal) and decanoato (Dec) complexes of the general formulas [Pt(Mal)(naza)2] (1-3) and cis-[Pt(Dec)2(naza)2] (4-7) were prepared, characterized and tested for their in vitro cytotoxicity against cisplatin-sensitive (A2780) and cisplatin-resistant (A2780R) human ovarian carcinoma cell lines and non-cancerous human lung fibroblasts (MRC-5); naza=halogeno-derivatives of 7-azaindole. Complexes 1-7 effectively overcome the acquired resistance of ovarian carcinoma cells to cisplatin. Complexes 2 (IC50=26.6±8.9μM against A2780 and 28.9±6.7μM against A2780R), 4 (IC50=14.5±0.6μM against A2780 and 14.5±3.8μM against A2780R) and 5 (IC50=13.0±1.1μM against A2780 and 13.6±4.9μM against A2780R) indicated decreased toxicity against healthy MRC-5 cells (IC50>50.0μM for 2 and >25.0μM for 4 and 5). The representative complexes 2 and 4 showed mutually different effect on the A2780 cell cycle at IC50 concentrations after 24h exposure. Concretely, the complex 2 caused cell cycle arrest at G0/G1 phase, while 4 induced cell death by apoptosis with high population of cells in sub-G1 cell cycle phase. The hydrolysis and interactions of the selected complexes with biomolecules (glutathione (GSH) and guanosine monophosphate (GMP)) were also studied by means of 1H NMR and ESI+ mass spectra.
References provided by Crossref.org
In vitro anticancer active cis-Pt(II)-diiodido complexes containing 4-azaindoles
