title: New palladium and platinum complexes with bioactive 3,5-diacetyl-1,2,4-triazol bis(4-cyclohexyl thiosemicarbazone) ligand: chemistry, antiproliferative activity and preliminary toxicity studies.
abstract: The preparation and characterization of the new 3,5-diacetyl-1,2,4-triazol bis(4-cyclohexyl thiosemicarbazone) ligand, H(5)L(1), is described. Treatment of H(5)L(1) with K(2)PtCl(4) gave the dinuclear complex [Pt(H(3)L(1))](2), 1, but using MCl(2)(PPh(3))(2) where M = Pd or Pt, mononuclear complexes 2 and 3, of general formula [M(H(3)L(1))PPh(3)], were obtained. Subsequent reaction of the [Pd(H(3)L(1))PPh(3)] complex with PdCl(2)(PPh(3))(2) yielded a new dinuclear complex [(PPh(3))Pd(H(2)L(1))PdCl], 4. All compounds have been characterized by elemental analysis and FAB(+) spectrometry and by IR and NMR spectroscopy. The molecular structures of mononuclear complexes 2 and 3 and dinuclear complex 4 have been determined by X-ray crystallography. The new compounds synthesized have been evaluated for antiproliferative activity in vitro against NCI-H460, HepG2, MCF-7, A2780 and A2780cisR human cancer cell lines. The cytotoxicity data suggest that the H(5)L(1) ligand and [Pt(H(3)L(1))](2), complex 1, may be endowed with important cytotoxic properties since they are capable of not only circumventing cisplatin resistance in A2780cisR but also exhibit antiproliferative activity in NCI-H460. The interactions of these compounds with calf thymus DNA were 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, 7, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Matesanz
authors.forename: Josefina
authors.initials: J
authors.lastname: Perles
authors.forename: Pilar
authors.initials: P
authors.lastname: Souza
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D018374:LLC-PK1 Cells; D008024:Ligands; D010165:Palladium / Q000737:chemistry* / Q000494:pharmacology; D010984:Platinum / Q000737:chemistry* / Q000494:pharmacology; D013552:Swine; D013882:Thiosemicarbazones / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D013882:Thiosemicarbazones; D010984:Platinum; D010165:Palladium; D004247:DNA; C427203:calf thymus DNA