title: DNA binding, nuclease activity, DNA photocleavage and cytotoxic properties of Cu(II) complexes of N-substituted sulfonamides.
abstract: Ternary copper(II) complexes [Cu(NST)2(phen)] (1) and [Cu(NST)2(NH3)2]·H2O (2) [HNST=N-(4,5-dimethylthiazol-2-yl)naphthalene-1-sulfonamide] were prepared and characterized by physico-chemical techniques. Both 1 and 2 were structurally characterized by X-ray crystallography. The crystal structures show the presence of a distorted square planar CuN4 geometry in which the deprotonated sulfonamide, acting as monodentate ligand, binds to the metal ion through the thiazole N atom. Both complexes present intermolecular π-π stacking interactions between phenanthroline rings (compound 1) and between naphthalene rings (compound 2). The interaction of the complexes with CT DNA was studied by means of thermal denaturation, viscosity measurements and fluorescence spectroscopy. The complexes display good binding propensity to the calf thymus DNA giving the order: 1>2. Complex 1, which has a higher capability for binding to DNA, showed better nuclease activity than 2 in the presence of ascorbate/H2O2. Both the kinetics and the mechanism of the DNA cleavage reaction were investigated. Furthermore, complex 1 showed efficient photo-induced DNA cleavage activity on irradiation with UV light in the absence of any external reagent. The UV light induced DNA cleavage follows a photo-redox pathway with generation of hydroxyl radicals as reactive species. In addition, the cytotoxic properties of both complexes (1 and 2) were evaluated in human cancer cells (HeLa, Caco-2 and MDA-468). The low IC50 values, in particular those against Caco-2, have indicated that the compounds can be considered as promising chemotherapeutic agents.
authors: Centro de Investigación Biomédica en Red de Enfermedades Raras, Valencia, Spain.
authors: José Luis
authors: JL
authors: García-Giménez
authors: Javier
authors: J
authors: Hernández-Gil
authors: Aloma
authors: A
authors: Martínez-Ruíz
authors: Alfonso
authors: A
authors: Castiñeiras
authors: Malva
authors: M
authors: Liu-González
authors: Federico V
authors: FV
authors: Pallardó
authors: Joaquín
authors: J
authors: Borrás
authors: Gloria
authors: G
authors: Alzuet Piña
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000737:chemistry; D001665:Binding Sites; D002417:Cattle; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003300:Copper / Q000737:chemistry*; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D053837:DNA Cleavage / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D017665:Hydroxyl Radical / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007700:Kinetics; D009281:Naphthalenes / Q000737:chemistry*; D010618:Phenanthrolines / Q000737:chemistry*; D055668:Photochemical Processes; D013449:Sulfonamides / Q000737:chemistry*; D014466:Ultraviolet Rays
chemical_list: D056831:Coordination Complexes; D003603:Cytotoxins; D009281:Naphthalenes; D010618:Phenanthrolines; D013449:Sulfonamides; D017665:Hydroxyl Radical; D003300:Copper; D004247:DNA; C427203:calf thymus DNA; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid