期刊
CHEMMEDCHEM
卷 5, 期 1, 页码 96-102出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.200900370
关键词
antitumor agents; enzyme inhibitors; gold complexes; medicinal chemistry; thioredoxin reductases
资金
- Swiss National Science Foundation [PZ00P2_121933]
- Swiss Confederation [C09.0027]
- Ministerio de Ciencio e Innovacion [CTQ2008-06716-CO3-01]
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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