Interaction of vanadium compounds with biomolecules

Vanadium compounds (VCs) have been proposed as antidiabetic, antiparasitic, spermicidal, antiviral, anti-HIV, antituberculosis, and antitumor potential drugs. In physiological conditions, the two most important oxidation states of vanadium are IV and V. Interconversion between these two oxidation states can take place and while V(IV) can be easily oxidized to V(V), this latter is reduced to V(IV) in the cellular environment. The main problem with V potential drugs is their absorption in the gastrointestinal tract (if these are orally administered) or their absorption across the cellular membranes (if these are intravenously administered); in fact V inorganic compounds are poorly adsorbed and, therefore, high doses must be administered to exert their pharmacological effects. At high concentrations these compounds exhibit potential toxic effects typical of transition metals. For this reason, less toxic and more easily adsorbed V compounds were developed and good results were obtained with neutral V(IV) compounds with VOL2 composition, where L is a bidentate anionic organic carrier ligand. The role of the carrier ligands is to modulate the hydro-lipophilicity balance, to make the compounds soluble in aqueous solutions but lipophilic enough to cross the biological membranes. In this regard, two V(IV) species , bis(maltolato)oxidovanadium(IV) (BMOV) and bis(ethylmaltolato)oxidovanadium(IV) (BEOV), became the benchmark complexes for new molecules with anti-diabetic action. BEOV arrived at phase IIa of the clinical trials , even though these have provisionally been abandoned. An important aspect related to the pharmacological effects of VCs is their interaction with biomolecules because this interaction can affect their capability to cross biological membranes and the concentration which can reach the biological targets where they exert their effects. With biomolecules here we refer to both high and low molecular mass components of the blood and cellular environment. In this chapter we will describe the interaction of VCs with proteins (albumin, transferrin, immunoglobulin G, hemoglobin, lysozyme etc.) and with low mass bioligands present both in the serum (for example, lactate, citrate, phosphates , oxalate, amino acids) and in the cellular environment (ATP, ADP, AMP, GSH). After this description it is possible to calculate the distribution of a vanadium containing drug once this enters in the bloodstream and hypothesize the role of the biomolecules in the transport of this drug to the target cells.