title: Thioredoxin reductase and cancer cell growth inhibition by organotellurium antioxidants.
abstract: Thioredoxin (Trx) expression is increased in several human primary cancers and the Trx/Trx reductase (TrxR) system therefore provides an attractive target for cancer drug development. Novel organotellurium antioxidants, especially a primitive analog of vitamin E (compound 1d) and compounds 7, 9 and 10--all carrying highly functionalized 4-(dialkylamino)phenyltelluro groups to secure high antioxidative capacity--were found to inhibit TrxR with IC50 values in the low micromolar range. Whereas antioxidant 1d also inhibited the growth of MCF-7 human breast cancer cells in culture at a similar level (IC50 = 1.8 microM), the other TrxR inhibitors were inactive in concentrations below about 10 M.
authors.affiliation: Department of Organic Chemistry, Institute of Chemistry, Uppsala University, Uppsala, Sweden. Lars.Engman@kemi.uu.se
authors.forename: Lars
authors.initials: L
authors.lastname: Engman
authors.forename: Nawaf
authors.initials: N
authors.lastname: Al-Maharik
authors.forename: Michael
authors.initials: M
authors.lastname: McNaughton
authors.forename: Anne
authors.initials: A
authors.lastname: Birmingham
authors.forename: Garth
authors.initials: G
authors.lastname: Powis
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D010084:Oxidation-Reduction; D013691:Tellurium / Q000737:chemistry / Q000494:pharmacology*; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors*; D013879:Thioredoxins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D013879:Thioredoxins; D013880:Thioredoxin-Disulfide Reductase; D013691:Tellurium