Biotransformation of oxidovanadium(IV) complexes with oxydiacetate and NN-heterocycles

Cancer is a leading cause of death that keeps on challenging researchers, despite the increase in survival rates due to improved cancer treatment and particularly more efficient drugs. Vanadium has shown insulin-enhancing and antitumor properties. Recently, VIVO-complexes containing oxydiacetate (oda) were reported to have antitumoral effects. In particular, VO(oda) showed anti-proliferative activity on human colon adenocarcinoma cells,;1 and VO(oda), VO(oda)(bipy) and VO(oda)(phen), where bipy stands for 2,2'-bipyridine and phen for 1,10-phenanthroline, caused concentration dependent inhibition of cell proliferation in osteosarcoma cells.2 Knowledge of the transformations that these complexes can undergo in biological media are of importance to understand their therapeutic action. It is of primary importance to evaluate drug binding under physiological conditions to human serum proteins, particularly transferrin (hTF) and albumin (HSA), as serum proteins play a key role in the pharmacokinetics of the drugs in the human body. In this work the binding of VO(oda)(H2O)2, VO(oda)(bipy) and VO(oda)(phen) to hTF and HSA are reported. Several techniques were used for this purpose, namely EPR, fluorescence and circular dichroism (CD) spectroscopy. CD and EPR evidence that all VIVO-complexes bind to hTF keeping at least one organic ligand in the coordination sphere. ICP studies supply further support to the spectroscopic studies.