title: Chemistry, antiproliferative activity and low nephrotoxicity of 3,5-diacetyl-1,2,4-triazol bis(4N-thiosemicarbazone) ligands and their platinum(II) complexes.
abstract: The preparation and characterization of 3,5-diacetyl-1,2,4-triazol bis(4,4-dimethylthiosemicarbazone) ligand, H(3)L(1), and its dinuclear platinum complex [Pt(mu-HL(1))](2) is described. The crystal and molecular structure of the platinum complex has been resolved by single crystal X-ray diffraction. The ligands coordinate, in an asymmetric dideprotonate form, to the platinum ions in a tridentate fashion (NNS) and S-bridging bonding modes. Thus the molecular units of the platinum complexes are stacked as dimers. The new compounds synthesized together with the analogous monosubstituted ligand 3,5-diacetyl-1,2,4-triazol bis(4-methylthiosemicarbazone) (H(5)L(2)) and its dinuclear platinum(ii) complex [Pt(mu-H(3)L(2))](2) have been evaluated for antiproliferative activity in vitro against NCI-H460, A2780 and A2780cisR human cancer cell lines. The cytotoxicity data suggest that these compounds may be endowed with important antitumor properties, especially H(3)L(1) and [Pt(mu-H(3)L(2))](2) since they not only circumvent cisplatin resistance in A2780cisR cells but also exhibit high antiproliferative activity in human non-small cell lung cancer NCI-H460 cells. Subsequent nephrotoxic study, in LLC-PK1 cells, show that the four compounds investigated exhibit very low nephrotoxicity with respect to cisplatin.
authors.affiliation: Departamento de Química Inorgánica (Módulo 07), Facultad de Ciencias, c/Francisco Tomás y Valiente no 7, Universidad Autónoma de Madrid, 28049, Madrid, Spain.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Matesanz
authors.forename: Céline
authors.initials: C
authors.lastname: Joie
authors.forename: Pilar
authors.initials: P
authors.lastname: Souza
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C553051:3,5-diacetyl-1,2,4-triazol bis(4,4-dimethylthiosemicarbazone); D000970:Antineoplastic Agents; D008024:Ligands; D009944:Organoplatinum Compounds; D013882:Thiosemicarbazones; D014230:Triazoles