Stabilities and Biological Activities of Vanadium Drugs: What is the Nature of the Active Species?

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 VV and/or VIV reaction 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. Short‐lived media presence: The anti‐cancer and anti‐parasitic efficacies of vanadium drugs are of increasing interest, but their reactivity in biological media is poorly understood. As discussed in this review, most of these drugs rapidly decompose in the media, with the active species being either VV and VIV complexes of media components, or cell‐permeable chelating ligands that act through binding to essential metal ions in the medium.