title: Platinum(II) carboxylato complexes containing 7-azaindoles as N-donor carrier ligands showed cytotoxicity against cancer cell lines.
abstract: 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 IC50concentrations after 24h exposure. Concretely, the complex 2 caused cell cycle arrest at G0/G1phase, while 4 induced cell death by apoptosis with high population of cells in sub-G1cell cycle phase. The hydrolysis and interactions of the selected complexes with biomolecules (glutathione (GSH) and guanosine monophosphate (GMP)) were also studied by means of1H NMR and ESI+ mass spectra.
authors.affiliation: Regional Centre of Advanced Technologies, Division of Biologically Active Complexes and Molecular Magnets, Faculty of Science, Palacký University, 17. listopadu 12, CZ771 46 Olomouc, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Štarha
authors.affiliation: Regional Centre of Advanced Technologies, Division of Biologically Active Complexes and Molecular Magnets, Faculty of Science, Palacký University, 17. listopadu 12, CZ771 46 Olomouc, Czech Republic. Electronic address: zdenek.travnicek@upol.cz.
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Trávníček
authors.affiliation: Regional Centre of Advanced Technologies, Division of Biologically Active Complexes and Molecular Magnets, Faculty of Science, Palacký University, 17. listopadu 12, CZ771 46 Olomouc, Czech Republic.
authors.forename: Lucia
authors.initials: L
authors.lastname: Pazderová
authors.affiliation: Regional Centre of Advanced Technologies, Division of Biologically Active Complexes and Molecular Magnets, Faculty of Science, Palacký University, 17. listopadu 12, CZ771 46 Olomouc, Czech Republic.
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Dvořák
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002264:Carboxylic Acids / Q000737:chemistry*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry*; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005978:Glutathione / Q000737:chemistry; D006157:Guanosine Monophosphate / Q000737:chemistry; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: C023422:7-azaindole dimer; D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D056831:Coordination Complexes; D007211:Indoles; D009944:Organoplatinum Compounds; D006157:Guanosine Monophosphate; D005978:Glutathione; D002945:Cisplatin
keywords: 7-Azaindole derivatives; Antitumour activity; Cell cycle; Decanoato; Malonato; Platinum(II) complexes