Abstract |
Gold(I) complexes bearing water-soluble phosphine ligands, including 1,3,5-triaza-7-phosphaadamantane (PTA), 3,7- diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1] nonane ( DAPTA), and sodium triphenylphosphine trisulfonate (TPPTS), in combination with thionate ligands, were screened for their antiproliferative activities against human ovarian cancer cell lines A2780 either sensitive or resistant to cisplatin. In addition, the compounds were screened for their inhibition of mammalian thioredoxin reductases (TrxR), enzymes that are overexpressed in many tumor cells and contribute to drug resistance. The gold(I)- phosphine complexes efficiently inhibited cytosolic and mitochondrial TrxRs at concentrations that did not affect the related oxidoreductase glutathione reductase (GR). Additional complementary information on the enzyme metallation process and potential gold binding sites was obtained through the application of a specific biochemical assay using a thiol-tagging reagent, BIAM ( biotin-conjugated iodoacetamide).
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Authors | Elena Vergara, Angela Casini, Francesca Sorrentino, Olivier Zava, Elena Cerrada, Maria Pia Rigobello, Alberto Bindoli, Mariano Laguna, Paul J Dyson |
Journal | ChemMedChem
(ChemMedChem)
Vol. 5
Issue 1
Pg. 96-102
(Jan 2010)
ISSN: 1860-7187 [Electronic] Germany |
PMID | 19937669
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 1,3,5-triaza-7-phosphaadamantane
- Antineoplastic Agents
- Bridged Bicyclo Compounds
- Coordination Complexes
- Ligands
- Organophosphorus Compounds
- Phosphines
- Sulfonic Acids
- triphenylphosphine-3,3',3''-trisulfonic acid
- Gold
- Glutathione Reductase
- Thioredoxin-Disulfide Reductase
- phosphine
- Adamantane
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Topics |
- Adamantane
(analogs & derivatives, chemistry)
- Antineoplastic Agents
(chemistry, toxicity)
- Bridged Bicyclo Compounds
(chemistry)
- Cell Line, Tumor
- Coordination Complexes
(chemistry, toxicity)
- Glutathione Reductase
(antagonists & inhibitors, metabolism)
- Gold
(chemistry)
- Humans
- Ligands
- Organophosphorus Compounds
(chemistry)
- Phosphines
(chemistry)
- Sulfonic Acids
(chemistry)
- Thioredoxin-Disulfide Reductase
(antagonists & inhibitors, metabolism)
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