Speciation in human blood of Metvan, a vanadium based potential anti-tumor drug.

Abstract

The first report on the anti-cancer activity of the compound Metvan, [VIVO(Me2phen)2(SO4)], where Me2phen is 4,7-dimethyl-1,10-phenanthroline, dates back to 2001. Although it was immediately identified as one of the most promising multitargeted anti-cancer V compounds, no development on the medical experimentation was carried out. One of the possible reasons is the lack of information on its speciation in aqueous solution and its thermodynamic stability, factors which influence the transport in the blood and the final form which reaches the target organs. To fill this gap, in this work the speciation of Metvan in aqueous solution and human blood was studied by instrumental (EPR, electronic absorption spectroscopy, ESI-MS and ESI-MS/MS), analytical (pH-potentiometry) and computational (DFT) methods. The results suggested that Metvan transforms at physiological pH into the hydrolytic species cis-[VO(Me2phen)2(OH)]+ and that both citrate and proteins (transferrin and albumin in the blood serum, and hemoglobin in the erythrocytes) form mixed complexes, denoted [VO(Me2phen)(citrH-1)]2- and VO-Me2phen-Protein with the probable binding of His-N donors. The measurements with erythrocytes suggest that Metvan is able to cross their membrane forming mixed species VO-Me2phen-Hb. The redox stability in cell culture medium was also examined, showing that ca. 60% is oxidized to VV after 5 h. Overall, the speciation of Metvan in the blood mainly depends on the V concentration: when it is larger than 50 μM, [VO(Me2phen)(citrH-1)]2- and VO-Me2phen-Protein are the major species, while for concentrations lower than 10 μM, (VO)(hTf) is formed and Me2phen is lost. Therefore, it is plausible that the pharmacological activity of Metvan could be due to the synergic action of free Me2phen, and VIVO and VVO/VVO2 species.

• Authors: Daniele Sanna, Valeria Ugone, Giovanni Micera, Péter Buglyó, Linda Bíró, Eugenio Garribba
• Journal: Dalton transactions (Cambridge, England : 2003) (Dalton Trans) Vol. 46 Issue 28 Pg. 8950-8967 (Jul 18 2017) ISSN: 1477-9234 [Electronic] England
• PMID: 28640312 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Organometallic Compounds
• bis(4,7-dimethyl-1,10-phenanthroline)sulfatooxovanadium(IV)
• Citric Acid
• Lactic Acid

Topics

• Antineoplastic Agents (blood, chemistry)
• Citric Acid (chemistry)
• Humans
• Hydrogen-Ion Concentration
• Lactic Acid (chemistry)
• Models, Molecular
• Molecular Conformation
• Organometallic Compounds (blood, chemistry)
• Quantum Theory