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.
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Authors | Riccardo Pettinari, Claudio Pettinari, Fabio Marchetti, Brian W Skelton, Allan H White, Laura Bonfili, Massimiliano Cuccioloni, Matteo Mozzicafreddo, Valentina Cecarini, Mauro Angeletti, Massimo Nabissi, Anna Maria Eleuteri |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 57
Issue 11
Pg. 4532-42
(Jun 12 2014)
ISSN: 1520-4804 [Electronic] United States |
PMID | 24793593
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Biphenyl Compounds
- Coordination Complexes
- Pyrazolones
- Ruthenium
- DNA
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Topics |
- Antineoplastic Agents
(chemical synthesis, chemistry, pharmacology)
- Apoptosis
(drug effects)
- Biphenyl Compounds
(chemical synthesis, chemistry, pharmacology)
- Cell Cycle
(drug effects)
- Cell Line, Tumor
- Coordination Complexes
(chemical synthesis, chemistry, pharmacology)
- DNA
(chemistry)
- Drug Screening Assays, Antitumor
- Humans
- Pyrazolones
(chemical synthesis, chemistry, pharmacology)
- Ruthenium
- Structure-Activity Relationship
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