title: Cobalt complexes bearing scorpionate ligands: synthesis, characterization, cytotoxicity and DNA cleavage.
abstract: A number of novel, water-stable redox-active cobalt complexes of the C-functionalized tripodal ligands tris(pyrazolyl)methane XC(pz)(3) (X = HOCH(2), CH(2)OCH(2)Py or CH(2)OSO(2)Me) are reported along with their effects on DNA. The compounds were isolated as air-stable solids and fully characterized by IR and FIR spectroscopies, ESI-MS(+/-), cyclic voltammetry, controlled potential electrolysis, elemental analysis and, in a number of cases, also by single-crystal X-ray diffraction. They showed moderate cytotoxicity in vitro towards HCT116 colorectal carcinoma and HepG2 hepatocellular carcinoma human cancer cell lines. This viability loss is correlated with an increase of tumour cell lines apoptosis. Reactivity studies with biomolecules, such as reducing agents, H(2)O(2), plasmid DNA and UV-visible titrations were also performed to provide tentative insights into the mode of action of the complexes. Incubation of Co(II) complexes with pDNA induced double strand breaks, without requiring the presence of any activator. This pDNA cleavage appears to be mediated by O-centred radical species.
authors.affiliation: Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Technical University of Lisbon, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors.forename: Telma F S
authors.initials: TF
authors.lastname: Silva
authors.forename: Luísa M D R S
authors.initials: LM
authors.lastname: Martins
authors.forename: M Fátima C
authors.initials: MF
authors.lastname: Guedes da Silva
authors.forename: Alexandra R
authors.initials: AR
authors.lastname: Fernandes
authors.forename: Ana
authors.initials: A
authors.lastname: Silva
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Borralho
authors.forename: Susana
authors.initials: S
authors.lastname: Santos
authors.forename: Cecília M P
authors.initials: CM
authors.lastname: Rodrigues
authors.forename: Armando J L
authors.initials: AJ
authors.lastname: Pombeiro
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003035:Cobalt / Q000737:chemistry* / Q000494:pharmacology; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D003460:Crystallization; D053837:DNA Cleavage; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D003035:Cobalt