期刊
METALLOMICS
卷 8, 期 5, 页码 532-541出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c6mt00002a
关键词
-
资金
- Fondazione Banco di Sardegna [U924.2014/AI.807.MGB, 2014.04439]
The interaction of the potential anti-tumor agent vanadocene dichloride ([Cp2VCl2] 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 (HPO42-, P2O74-, cAMP, AMP, ADP and ATP) and carboxylate derivatives (lactate) and its uptake by red blood cells were studied. The results indicated that [Cp2VCl2] transforms at physiological pH into [Cp2V(OH)(2)] and that only HPO42-, P2O74-, lactate, ATP and ADP form mixed species with the [Cp2V](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 (VO)-O-IV species with loss of the two cyclopentadienyl rings. This transformation in the cellular environment could be related to the mechanism of action of VDC.
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