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 caspase activity, with consequent DNA fragmentation, accumulation of pro-apoptotic proteins (p27, p53, p89 PARP fragments), and the concomitant down-regulation of antiapoptotic 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 characterized the nature of the interaction. © 2014 American Chemical Society.
Arene-ruthenium(II) acylpyrazolonato complexes: Apoptosis-promoting effects on human cancer cells / Pettinari, R.; Pettinari, C.; Marchetti, F.; Skelton, B. W.; White, A. H.; Bonfili, L.; Cuccioloni, M.; Mozzicafreddo, M.; Cecarini, V.; Angeletti, M.; Nabissi, M.; Eleuteri, A. M.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 57:11(2014), pp. 4532-4542. [10.1021/jm500458c]
Arene-ruthenium(II) acylpyrazolonato complexes: Apoptosis-promoting effects on human cancer cells
Mozzicafreddo M.;
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 caspase activity, with consequent DNA fragmentation, accumulation of pro-apoptotic proteins (p27, p53, p89 PARP fragments), and the concomitant down-regulation of antiapoptotic 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 characterized the nature of the interaction. © 2014 American Chemical Society.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
