title: Gold(I) thiotetrazolates as thioredoxin reductase inhibitors and antiproliferative agents.
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.
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstrasse 55, 38106 Braunschweig, Germany. ingo.ott@tu-bs.de.
authors.forename: Tatiyana V
authors.initials: TV
authors.lastname: Serebryanskaya
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Lyakhov
authors.forename: Ludmila S
authors.initials: LS
authors.lastname: Ivashkevich
authors.forename: Julia
authors.initials: J
authors.lastname: Schur
authors.forename: Corazon
authors.initials: C
authors.lastname: Frias
authors.forename: Aram
authors.initials: A
authors.lastname: Prokop
authors.forename: Ingo
authors.initials: I
authors.lastname: Ott
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D018360:Crystallography, X-Ray; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D006046:Gold / Q000737:chemistry*; D019073:HT29 Cells; D006801:Humans; D008968:Molecular Conformation; D010720:Phosphines / Q000737:chemistry; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004791:Enzyme Inhibitors; D010720:Phosphines; D006046:Gold; D013880:Thioredoxin-Disulfide Reductase; C044646:phosphine