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Influence of PPh3 moiety in the anticancer activity of new organometallic ruthenium complexes

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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, and an important increment of the antitumor activity and cytotoxicity of the complexes due to the presence of PPh3 moiety has been demonstrated, affording IC50 values of 5.2 μM in HL-60 tumour 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, HPLC-MS studies have confirmed a strong interaction between Ruthenium complexes and proteins (Ubiquitin and Potato Carboxypeptidase Inhibitor -PCI-) including slower kinetic 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 change in the structural conformation of the proteins owing to their bonding to Ruthenium complexes. This seems particularly important in the case of PCI, that may be a suitable candidate for vehiculizing these complexes in a selective manner into tumour cells. In agreement with these results, further investigations should be carried out to clarify either there is a favoured binding to DNA or to specific proteins, thus to elucidate their main biological target.

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Journal of Inorganic Biochemistry, 2014, vol. 136, p. 1-12

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Articles publicats en revistes (Mineralogia, Petrologia i Geologia Aplicada)

# metadata.dc.title[].value
Influence of PPh3 moiety in the anticancer activity of new organometallic ruthenium complexes