Biotransformation in the blood serum of potential antitumor V(IV)O2+ complexes and interaction with red blood cells

Oxidovanadium(IV) complexes of flavonoids were shown to be promising antitumor agents against several cancer cell lines. Despite these promising effects little or nothing is known about their mechanism of action and biotransformation in the blood. This latter aspect is important in the evaluation of the transport and drug metabolism. Indeed, in the blood, ligand exchange and complexation reactions by the components of the plasma and red blood cells are possible; moreover, a V(IV)O2+ compound can distribute between plasma and erythrocytes with the consequence that a significant fraction of the complex can be transported toward the target organs by the red blood cells and that the transformation in the cytosol can partly or totally deactivate the V drug. The chemical form with which a vanadium compound reaches the target organs affects the uptake by the cells, which can take place through passive diffusion or be mediated by receptors. Recently some of us demonstrated that flavonoid ligands can be grouped in three classes on the basis of the type of V(IV)O2+ complex formed under physiological conditions: i) flavonoids such as chrysin and morin form penta-coordinated species with (CO, O-) donor set and "acetylacetone-like" coordination; ii) flavonoids such as fisetin and quercetin form anionic V(IV)O2+ penta-coordinated complexes with (O-, O-) set and "catechol-like" coordination; iii) flavonoids such as 3-hydroxyflavone form neutral hexa-coordinated species with cis-octahedral geometry and (CO, O-) donor set and "maltol-like" coordination. The interaction of oxidovanadium(IV) complexes formed by flavonoids with high and low molecular mass components of the blood serum (transferrin and albumin among the former, lactate and citrate between the latter) was evaluated and the results will be presented. Moreover the interaction with erythrocytes was studied to determine if these complexes are able to cross the cell wall and undergo ligand exchange and/or redox reactions as recently shown by some of us for antidiabetic V(IV)O2+ complexes.