title: Influence of PPh₃ moiety in the anticancer activity of new organometallic ruthenium complexes.
abstract: The effect of the PPh3 group in the antitumor activity of some new organometallic ruthenium(II) complexes has been investigated. Several complexes of the type [Ru((II))(Cl)(PPh3)(Lig-N)], [Ru((II))(Cl)2(Lig-N)] (where Lig-N=pyridine derivate) and [Ru((II))(Cl)(PPh3)2], have been synthesized and characterized. A noticeable increment of the antitumor activity and cytotoxicity of the complexes due to the presence of PPh3 moiety has also been demonstrated, affording IC50 values of 5.2 μM in HL-60 tumor cell lines. Atomic force microscopy, circular dichroism and electrophoresis experiments have proved that these complexes can bind DNA resulting in a distortion of both secondary and tertiary structures. Ethidium bromide displacement fluorescence spectroscopy studies and viscosity measurements support that the presence of PPh3 group induces intercalation interactions with DNA. Indeed, crystallographic analysis, suggest that intra-molecular π-π interactions could be involved in the intercalation within DNA base pairs. Furthermore, high performance liquid chromatography mass spectrometry (HPLC-MS) studies have confirmed a strong interaction between ruthenium complexes and proteins (ubiquitin and potato carboxypeptidase inhibitor - PCI) including slower kinetics due to the presence of PPh3 moiety, which could have an important role in detoxification mechanism and others. Finally, ion mobility mass spectrometry (IMMS) experiments have proved that there is no significant change in the gas phase structural conformation of the proteins owing to their bonding to ruthenium complexes.
authors.affiliation: Department de Química Inorgànica, Facultat de Química, Universitat de Barcelona, Martí y Franquès 1-11, 08028 Barcelona, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Sáez
authors.affiliation: Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Lorenzo
authors.affiliation: Departament de Microbiologia, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, 08028 Barcelona, Spain.
authors.forename: Ma Jose
authors.initials: MJ
authors.lastname: Prieto
authors.affiliation: Departament de Cristal·lografia, Mineralogia i Dipòsits Minerals, Universitat de Barcelona, Martí i Franquès s/n., 08028 Barcelona, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Font-Bardia
authors.affiliation: Departament de Cristal·lografia, Mineralogia i Dipòsits Minerals, Universitat de Barcelona, Martí i Franquès s/n., 08028 Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Calvet
authors.affiliation: IRB Barcelona-Institute for Research in Biomedicine, Parc Científic de Barcelona, Baldiri Reixac, 10-12, 08028 Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Omeñaca
authors.affiliation: IRB Barcelona-Institute for Research in Biomedicine, Parc Científic de Barcelona, Baldiri Reixac, 10-12, 08028 Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Vilaseca
authors.affiliation: Department de Química Inorgànica, Facultat de Química, Universitat de Barcelona, Martí y Franquès 1-11, 08028 Barcelona, Spain. Electronic address: virtudes.moreno@qi.ub.es.
authors.forename: Virtudes
authors.initials: V
authors.lastname: Moreno
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008968:Molecular Conformation; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010957:Plasmids / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014783:Viscosity
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D009943:Organophosphorus Compounds; C061896:triphenylphosphine; D012428:Ruthenium; D004247:DNA; C427203:calf thymus DNA
keywords: Arene ruthenium(II) complexes; Calf thymus DNA; DNA interaction; Protein interaction; Ruthenium antitumor compounds; pBR322 DNA