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., H VO ) 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 V and/or V 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.

Vanadium: History, chemistry, interactions with α-amino acids and potential therapeutic applications

“…In previous sections, we have described the importance of vanadium at industrial level, the chemical speciation of binary and ternary complexes with amino acids and very briefly their importance at the biological level. The studies of chemical speciation in aqueous solution are fundamental to know the nature, abundance and stability of the different species in solution, because they represent an essential requirement to evaluate the biological activity of promising therapeutic targets [121][122][123][124][125][126]. In this section we will discuss the applications of vanadium compounds, especially vanadium complexes with (non)essential amino acids, in pharmacology and medical therapeutics, as well as their importance in bioinorganic chemistry.…”

A Short‐Lived but Highly Cytotoxic Vanadium(V) Complex as a Potential Drug Lead for Brain Cancer Treatment by Intratumoral Injections

“…[1a,c] In the past, the extensive reactivity of V complexes in biological media and the associated toxicity has been regarded as the main obstacle to their translation into clinical practice. [5] We propose that the limited lifetime of typical V complexes in biological media can be turned into an advantage for their use in intratumoral injections. Such drugs begin to kill cancer cells immediately after injection into the tumor, while their decomposition products released into the blood are less toxic.…”

“…This is expected to reduce systemic toxicity that is a major problem of chemotherapy. [6] Furthermore, these decomposition products are likely to prove beneficial, given the known antidiabetic, [3,5] anti-mutagenic, [7] tissue regeneration promoting, [8] and neuro-stimulatory [9] properties of V compounds, all of which can provide simultaneous benefits to many patients.…”

Ruthenium(II)–Arene Thiocarboxylates: Identification of a Stable Dimer Selectively Cytotoxic to Invasive Breast Cancer Cells

“…Complexes 1 – 7 retained dimeric structures under biomimetic conditions (50 μ m Ru, 10 m m aqueous NH 4 HCO 3 , pH 7.5, stored for up to a week at 295 K), as shown by ESI‐MS (Figure S8). These results contrast those for typical metal complexes that rapidly decompose under cell culture conditions . Stock solutions of 1 – 7 used in the ESI‐MS studies (2–20 m m Ru in DMF) were stored for about a month in the dark at 295 K prior to the dilution with 10 m m NH 4 HCO 3 .…”