Biorelevant reactions of the potential anti-tumor agent vanadocene dichloride. Issue 5 (28th April 2016)

• Record Type: Journal Article
• Authors: Sanna, Daniele; Serra, Maria; Ugone, Valeria; Manca, Laura; Pirastru, Monica; Buglyó, Péter; Bíró, Linda; Micera, Giovanni; Garribba, Eugenio
• Is Part Of: Metallomics. Volume 8:Issue 5(2016:May)
• Page Start: 532
• Page End: 541
• Publication Date: 2016-04-28
• Subjects: Metals -- Physiological effect -- Periodicals; 572.51
• DOI: 10.1039/c6mt00002a
• Languages: English
• ISSNs: 1756-5901

Abstract

Abstract : The interaction of the potential anti-tumor agent vanadocene dichloride ([Cp2 VCl2 ] or VDC) with some relevant bioligands of the cytosol and its uptake by red blood cells were studied. Abstract : The interaction of the potential anti-tumor agent vanadocene dichloride ([Cp2 VCl2 ] or VDC) with some relevant bioligands of the cytosol such as proteins (Hb), amino acids (glycine and histidine), NADH derivatives (NADH, NADPH, NAD + and NADP + ), reductants (GSH and ascorbic acid), phosphates (HPO4 2−, P2 O7 4−, cAMP, AMP, ADP and ATP) and carboxylate derivatives (lactate) and its uptake by red blood cells were studied. The results indicated that [Cp2 VCl2 ] transforms at physiological pH into [Cp2 V(OH)2 ] and that only HPO4 2−, P2 O7 4−, lactate, ATP and ADP form mixed species with the [Cp2 V] 2+ moiety replacing the two hydroxide ions. EPR and electronic absorption spectroscopy, agarose gel electrophoresis and spin trapping measurements allow excluding any direct interaction and/or intercalation with DNA and the formation of reactive oxygen species (ROS) in Fenton-like reactions. Uptake experiments by erythrocytes suggested that VDC crosses the membrane and enters inside the cells, whereas 'bare' V IV transforms into V IV O species with loss of the two cyclopentadienyl rings. This transformation in the cellular environment could be related to the mechanism of action of VDC.