Gold(I) thiotetrazolates as thioredoxin reductase inhibitors and antiproliferative agents

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 cyto...

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Veröffentlicht in:	Dalton transactions : an international journal of inorganic chemistry 2015-01, Vol.44 (3), p.1161-1169
Hauptverfasser:	Serebryanskaya, Tatiyana V, Lyakhov, Alexander S, Ivashkevich, Ludmila S, Schur, Julia, Frias, Corazon, Prokop, Aram, Ott, Ingo
Format:	Artikel
Sprache:	eng
Schlagworte:	Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - toxicity Antiproliferatives Cell Line, Tumor Cell Proliferation - drug effects Cellular Colon Coordination Complexes - chemical synthesis Coordination Complexes - chemistry Coordination Complexes - toxicity Crystallography, X-Ray Drug Resistance, Neoplasm - drug effects Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - chemistry Enzyme Inhibitors - toxicity Gold Gold - chemistry HT29 Cells Humans Inhibitors Ligands Molecular Conformation Phosphines - chemistry Reductases Thioredoxin-Disulfide Reductase - antagonists & inhibitors Thioredoxin-Disulfide Reductase - metabolism Uptakes
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Zusammenfassung:	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.
ISSN:	1477-9226 1477-9234
DOI:	10.1039/c4dt03105a