title: Stabilities and Biological Activities of Vanadium Drugs: What is the Nature of the Active Species?
abstract: Diverse biological activities of vanadium(V) drugs mainly arise from their abilities to inhibit phosphatase enzymes and to alter cell signaling. Initial interest focused on anti-diabetic activities but has shifted to anti-cancer and anti-parasitic drugs. V-based anti-diabetics are pro-drugs that release active components (e.g., H2VO4-) in biological media. By contrast, V anti-cancer drugs are generally assumed to enter cells intact; however, speciation studies indicate that nearly all drugs are likely to react in cell culture media during in vitro assays and the same would apply in vivo. The biological activities are due to VVand/or VIVreaction products with cell culture media, or the release of ligands (e.g., aromatic diimines, 8-hydroxyquinolines or thiosemicarbazones) that bind to essential metal ions in the media. Careful consideration of the stability and speciation of V complexes in cell culture media and in biological fluids is essential to design targeted V-based anti-cancer therapies.
authors.affiliation: School of Chemistry, University of Sydney, Sydney, 2006 NSW, Australia.
authors.forename: Aviva
authors.identifier: http://orcid.org/0000-0002-7311-3263
authors.initials: A
authors.lastname: Levina
authors.affiliation: School of Chemistry, University of Sydney, Sydney, 2006 NSW, Australia.
authors.forename: Peter A
authors.identifier: http://orcid.org/0000-0002-3232-2720
authors.initials: PA
authors.lastname: Lay
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014639:Vanadium / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D009942:Organometallic Compounds; D011355:Prodrugs; D014639:Vanadium
keywords: cancer; cytotoxicity; diabetes; speciation; vanadium