A series of ruthenium(II) arene complexes with the 4-(biphenyl-4-carbonyl)-3-methyl-1-phenyl-5-pyrazolonate ligand, and related 1,3,5-triaza-7-phosphaadamantane (PTA) derivatives has been synthesized. The compounds have been characterized by NMR and IR spectroscopy, ESI mass spectrometry, elemental analysis, and X-ray crystallography. Antiproliferative activity in four human cancer cell lines was determined by MTT assay, yielding dose- and cancer cell line-dependent IC50 values of 9-34 μM for three hexamethylbenzene-ruthenium complexes, whereas the other metal complexes were much less active. Apoptosis was the mechanism involved in the anticancer activity of such compounds. In fact, the hexamethylbenzene-ruthenium complexes activated caspases activity, with consequent DNA fragmentation, accumulation of pro-apoptotic proteins (p27, p53, p89 PARP fragments), and the concomitant down-regulation of anti-apoptotic protein Bcl-2. Biosensor based binding studies indicated that the ancillary ligands were critical in determining the DNA binding affinities, and competition binding experiments further characterize the nature of the interaction.

Arene–Ruthenium(II) Acylpyrazolonato Complexes: Apoptosis-Promoting Effects on Human Cancer Cells

PETTINARI, Riccardo;PETTINARI, Claudio;MARCHETTI, Fabio;BONFILI, LAURA;CUCCIOLONI, Massimiliano;MOZZICAFREDDO, MATTEO;CECARINI, Valentina;ANGELETTI, Mauro;NABISSI, MASSIMO;ELEUTERI, Anna Maria
2014-01-01

Abstract

A series of ruthenium(II) arene complexes with the 4-(biphenyl-4-carbonyl)-3-methyl-1-phenyl-5-pyrazolonate ligand, and related 1,3,5-triaza-7-phosphaadamantane (PTA) derivatives has been synthesized. The compounds have been characterized by NMR and IR spectroscopy, ESI mass spectrometry, elemental analysis, and X-ray crystallography. Antiproliferative activity in four human cancer cell lines was determined by MTT assay, yielding dose- and cancer cell line-dependent IC50 values of 9-34 μM for three hexamethylbenzene-ruthenium complexes, whereas the other metal complexes were much less active. Apoptosis was the mechanism involved in the anticancer activity of such compounds. In fact, the hexamethylbenzene-ruthenium complexes activated caspases activity, with consequent DNA fragmentation, accumulation of pro-apoptotic proteins (p27, p53, p89 PARP fragments), and the concomitant down-regulation of anti-apoptotic protein Bcl-2. Biosensor based binding studies indicated that the ancillary ligands were critical in determining the DNA binding affinities, and competition binding experiments further characterize the nature of the interaction.
2014
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/315181
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