Titanocene Y and Vanadocene Y: Platinum Resistance-Breaking Cytotoxic and DNA-Targeting Anticancer Drug Candidates
About: This article is published in Letters in Drug Design & Discovery.The article was published on 2011-11-30. It has received 8 citations till now. The article focuses on the topics: Vanadocene.
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07 Feb 2019
40 citations
01 Dec 2016
TL;DR: In this paper, 30 new β-diketonate titanium compounds of the type [Ti(O,O)2X2], whereby O,O=asymmetric or symmetric β-Diketonates ligand and X=Cl, Br, OEt or OiPr.
Abstract: Herein, we report 30 new β-diketonate titanium compounds of the type [Ti(O,O)2X2], whereby O,O=asymmetric or symmetric β-diketonate ligand and X=Cl, Br, OEt or OiPr. Thirteen new crystal structures are discussed and show that these octahedral species all adopt cis geometries in the solid state. These compounds have been tested for their cytotoxicity using SRB and MTT assays, showing several of the compounds are as potent as cisplatin against a range of tumor cell lines. Results also show the [Ti(O,O)2Br2] complexes are more potent than [Ti(O,O)2Cl2], [Ti(O,O)2(OEt)2] and [Ti(O,O)2(OiPr)2]. Using a simple symmetrical heptane-3,5-dione (O,O) ligand bound to titanium, we observed more than a 50-fold increase in potency with the [Ti(O,O)2Br2] (28) when compared to [Ti(O,O)2Cl2] (27). One of the more potent compounds (6) has been added to three different sixmers of DNA, in order to analyse the potential DNA binding of the compound. NMR studies have been carried out on the compounds, in order to understand the structural properties and the species formed in solution during the in vitro cell assays.
12 citations
TL;DR: The effect of the compounds on cytotoxicity, cell adhesion and migration of the androgen-independent prostate cancer PC-3 cells has been assessed and interactions of the novel compounds with plasmid DNA have been studied, showing that the oximato Ti(IV) derivatives have a weak or no interaction with DNA at physiological pH.
11 citations
TL;DR: 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, which could be related to the mechanism of action of VDC.
Abstract: 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’ VIV transforms into VIVO species with loss of the two cyclopentadienyl rings. This transformation in the cellular environment could be related to the mechanism of action of VDC.
11 citations
TL;DR: In this paper, the synthesis of vanadocene compounds was described, where Cp′ is substituted cyclopentadienyl ring and L is N, N -chelating ligand.
9 citations