Abstract
Gold(i) complexes with phosphane and thiotetrazolate ligands were prepared and investigated as a new type of bioactive gold metallodrugs. The complexes triggered very efficient inhibition of the enzyme thioredoxin reductase (TrxR), which is an important molecular target for gold species. Strong cytotoxic effects were observed in MDA-MB-231 breast adenocarcinoma and HT-29 colon carcinoma cells, and the complexes also caused strong effects in vincristine resistant Nalm-6 leukemia cells. Cellular uptake studies showed elevated cellular gold levels for complexes containing a triphenylphosphane ligand, whereas trifurylphosphane analogues accumulated at significantly lower cellular concentrations.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / toxicity
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Coordination Complexes / chemical synthesis
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Coordination Complexes / chemistry*
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Coordination Complexes / toxicity
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Crystallography, X-Ray
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Drug Resistance, Neoplasm / drug effects
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / toxicity
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Gold / chemistry*
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HT29 Cells
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Humans
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Molecular Conformation
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Phosphines / chemistry
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Thioredoxin-Disulfide Reductase / antagonists & inhibitors*
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Thioredoxin-Disulfide Reductase / metabolism
Substances
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Antineoplastic Agents
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Coordination Complexes
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Enzyme Inhibitors
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Phosphines
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Gold
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Thioredoxin-Disulfide Reductase
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phosphine