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Published on: March 18, 2015
Gold(I) thiotetrazolates as thioredoxin reductase inhibitors and antiproliferative agents
Tatiyana V Serebryanskaya1, Alexander S Lyakhov, Ludmila S Ivashkevich
1Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstrasse 55, 38106 Braunschweig, Germany. ingo.ott@tu-bs.de.
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.
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