The first report on the potential anti-cancer action of a vanadium compound concerns vanadocene dichloride, abbreviated here with VDC. It is active in the treatment of Ehrlich ascites tumor and a very active derivative of VDC is [(pmethoxybenzyl) cyclopentadienyl]vanadium(IV) dichloride (vanadocene Y), which exhibits an IC50 value of 3.0 microM against the LLC-PK (pig kidney epithelial) cell line. Vanadocene Y is slightly more active against this cell line than the 'classic' cisplatin, which shows an IC50 value of 3.3 microM. The biotransformation of a pharmacologically active metal complex in the blood is an important aspect of the drug metabolism, and the form transported to the target organs significantly affects its efficiency and mechanism of action. All the main proteins of the plasma, such as transferrin (hTf), albumin (HSA) and immunoglobulin G (IgG), and the low molecular mass bioligands, such as oxalate, lactate, phosphate, citrate, amino acids, can interact with the V compound administered and can displace (partly or fully) the organic ligands. In this work, the interaction of VDC with several components of the blood serum was studied through the combined application of spectroscopic (EPR and electronic absorption spectroscopy) and computational (DFT) methods, which are valid tools to explore vanadium(IV) chemistry. A particular importance assume the results of the measurements under physiological conditions (pH ca. 7.4).
Interaction of vanadocene dichloride with the blood serum components
Daniele Sanna;Valeria Ugone;Eugenio Garribba
2015
Abstract
The first report on the potential anti-cancer action of a vanadium compound concerns vanadocene dichloride, abbreviated here with VDC. It is active in the treatment of Ehrlich ascites tumor and a very active derivative of VDC is [(pmethoxybenzyl) cyclopentadienyl]vanadium(IV) dichloride (vanadocene Y), which exhibits an IC50 value of 3.0 microM against the LLC-PK (pig kidney epithelial) cell line. Vanadocene Y is slightly more active against this cell line than the 'classic' cisplatin, which shows an IC50 value of 3.3 microM. The biotransformation of a pharmacologically active metal complex in the blood is an important aspect of the drug metabolism, and the form transported to the target organs significantly affects its efficiency and mechanism of action. All the main proteins of the plasma, such as transferrin (hTf), albumin (HSA) and immunoglobulin G (IgG), and the low molecular mass bioligands, such as oxalate, lactate, phosphate, citrate, amino acids, can interact with the V compound administered and can displace (partly or fully) the organic ligands. In this work, the interaction of VDC with several components of the blood serum was studied through the combined application of spectroscopic (EPR and electronic absorption spectroscopy) and computational (DFT) methods, which are valid tools to explore vanadium(IV) chemistry. A particular importance assume the results of the measurements under physiological conditions (pH ca. 7.4).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
