Anticancer therapeutics that target selenoenzymes: synthesis, characterization, in vitro cytotoxicity, and thioredoxin reductase inhibition of a series of gold(I) complexes containing hydrophilic phosphine ligands.

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).
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)
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
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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