title: trans-thionate derivatives of Pt(II) and Pd(II) with water-soluble phosphane PTA and DAPTA ligands: antiproliferative activity against human ovarian cancer cell lines.
abstract: A series of PTA and DAPTA platinum(II) and palladium(II) thionate complexes of the type trans-[M(SN)2P2] were prepared from the reaction of cis-[MCl2P2] [M = Pt, Pd; P = PTA (1,3,5-triaza-7-phosphaadamantane), DAPTA (3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane)] with the in situ generated sodium salts of the heterocyclic thiones S-m-methylpyrimidine-2-thione, S-4,6-dimethylpyrimidine-2-thione, S-4,6-dihydroxypyrimidine-2-thione, benzothiazole-2-thione, benzoxazole-2-thione, S-1,3,4,-thiadiazole-2-thione, S-4,5-H-thiazolan-2-thione, and S-pyrimidine-4(1H)-one-2-thione. The X-ray structures of six of the compounds confirm the trans disposition and, only in the case of [Pd2Cl2(S-pyrimidine-4(1H)-one-2-thionate)2(PTA)2], a dinuclear structure with a Pd-Pd distance of 3.0265(14)Å was observed. In vitro cytotoxicities against human ovarian cancer cell lines A2780 and A2780cisR were evaluated for ten complexes showing a high inhibition of cellular growth with a comparable inhibitory potency (IC50) against A2780 cells to that of cisplatin. Notably, the compounds also show significant (up to 7-fold higher) activity in cisplatin-resistant A2780cisR cell lines.
authors.affiliation: Departamento de Química, Área de Química Inorgánica, Facultad de Ciencias, Universidad de Burgos, 09001 Burgos, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Guerrero
authors.forename: Susana
authors.initials: S
authors.lastname: Miranda
authors.forename: Sebastian
authors.initials: S
authors.lastname: Lüttenberg
authors.forename: Nils
authors.initials: N
authors.lastname: Fröhlich
authors.forename: Jan-Moritz
authors.initials: JM
authors.lastname: Koenen
authors.forename: Fabian
authors.initials: F
authors.lastname: Mohr
authors.forename: Elena
authors.initials: E
authors.lastname: Cerrada
authors.forename: Mariano
authors.initials: M
authors.lastname: Laguna
authors.forename: Aránzazu
authors.initials: A
authors.lastname: Mendía
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry; D010984:Platinum / Q000737:chemistry; D012995:Solubility; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: C501763:1,3,5-triaza-7-phosphaadamantane; C585298:3,7-triaza-5-phosphabicyclo(3.3.1)nonane; D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D008024:Ligands; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D013438:Sulfhydryl Compounds; D014867:Water; D010984:Platinum; D010165:Palladium; D000218:Adamantane