Chemistry, antiproliferative properties, tumor selectivity, and molecular mechanisms of novel gold(III) compounds for cancer treatment: a systematic study.
- Casini A Laboratory of Organometallic and Medicinal Chemistry, Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. angela.casini@epfl.ch
- Kelter G
- Gabbiani C
- Cinellu MA
- Minghetti G
- Fregona D
- Fiebig HH
- Messori L
- 2009-06-23
Published in:
- Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry. - 2009
Antineoplastic Agents
Cell Line, Tumor
Cell Proliferation
Drug Screening Assays, Antitumor
Electrochemical Techniques
Gold Compounds
Humans
Indicators and Reagents
Inhibitory Concentration 50
Molecular Conformation
Propidium
Spectrophotometry
Statistics, Nonparametric
Structure-Activity Relationship
English
The antiproliferative properties of a group of 13 structurally diverse gold(III) compounds, including six mononuclear gold(III) complexes, five dinuclear oxo-bridged gold(III) complexes, and two organogold(III) compounds, toward several human tumor cell lines were evaluated in vitro using a systematic screening strategy. Initially all compounds were tested against a panel of 12 human tumor cell lines, and the best performers were tested against a larger 36-cell-line panel. Very pronounced antiproliferative properties were highlighted in most cases, with cytotoxic potencies commonly falling in the low micromolar--and even nanomolar--range. Overall, good-to-excellent tumor selectivity was established for at least seven compounds, making them particularly attractive for further pharmacological evaluation. Compare analysis suggested that the observed antiproliferative effects are caused by a variety of molecular mechanisms, in most cases "DNA-independent," and completely different from those of platinum drugs. Remarkably, some new biomolecular systems such as histone deacetylase, protein kinase C/staurosporine, mammalian target of rapamycin/rapamycin, and cyclin-dependent kinases were proposed for the first time as likely biochemical targets for the gold(III) species investigated. The results conclusively qualify gold(III) compounds as a promising class of cytotoxic agents, of outstanding interest for cancer treatment, while providing initial insight into their modes of action.
- Language
-
- English
- Open access status
- green
- Identifiers
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- DOI 10.1007/s00775-009-0558-9
- PMID 19543922
- Persistent URL
- https://sonar.ch/global/documents/16130
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