title: Novel bis(thiosemicarbazones) of the 3,5-diacetyl-1,2,4-triazol series and their platinum(II) complexes: chemistry, antiproliferative activity and preliminary nephrotoxicity studies.
abstract: The preparation and characterization of three novel (4)N-monosubstituted bis(thiosemicarbazone) ligands of 3,5-diacetyl-1,2,4-triazol series and their dinuclear platinum complexes are described. The crystal and molecular structure of the [Pt(μ-H(3)L(3))](2) complex derived of 3,5-diacetyl-1,2,4-triazol bis((4)N-p-tolylthiosemicarbazone), H(5)L(3), 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 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 antitumour properties since are capable of not only circumventing cisplatin resistance in A2780cisR cells but also exhibit high antiproliferative activity in human non-small cell lung cancer NCI-H460 cells. The interactions of these compounds with calf thymus DNA was investigated by UV-vis absorption and a nephrotoxic study, in LLC-PK1 cells, has also been carried out.
authors.affiliation: Departamento de Química Inorgánica (Módulo 07), Facultad de Ciencias, c/Francisco Tomás y Valiente n° 7, Universidad Autónoma de Madrid, 28049, Madrid, Spain.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Matesanz
authors.forename: Carolina
authors.initials: C
authors.lastname: Hernández
authors.forename: Ana
authors.initials: A
authors.lastname: Rodríguez
authors.forename: Pilar
authors.initials: P
authors.lastname: Souza
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D002417:Cattle; D002460:Cell Line; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry* / Q000633:toxicity; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D003931:Diacetyl / Q000737:chemistry; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D008968:Molecular Conformation; D010984:Platinum / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013882:Thiosemicarbazones / Q000737:chemistry*; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D013882:Thiosemicarbazones; D014230:Triazoles; C045575:1,2,4-triazole; D010984:Platinum; D004247:DNA; C427203:calf thymus DNA; D003931:Diacetyl