Electrochemical evaluation of the interaction between antitumoral titanocene dichloride and biomolecules

Ravera, Mauro; Gabano, Elisabetta; Baracco, Sara; Osella, Domenico

doi:10.1016/j.ica.2008.06.022

Cited by 23 publications

(26 citation statements)

References 33 publications

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“…55 Although initial studies suggested that the effect of titanocene derivatives might be related to DNA interaction, 56 later investigations indicate that metallocene dihalides neither bind strongly to DNA at neutral pH nor suppress DNA-processing enzymes. 57 More recent reports provide experimental evidence of titanium being accumulated in the cellular nucleic acid-rich regions, particularly in the chromatin. 58 Moreover it has been suggested that Cp 2 TiCl 2 or, more likely, Ti(IV) ions can interact weakly with the phosphate groups of nucleotides at neutral pH.…”

Section: Resultsmentioning

confidence: 99%

Titanocene–Phosphine Derivatives as Precursors to Cytotoxic Heterometallic TiAu₂and TiM (M = Pd, Pt) Compounds. Studies of Their Interactions with DNA

et al. 2011

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A series of tri- and bimetallic titanium-gold, titanium-palladium and titanium-platinum derivatives of general formulas [Ti{η5-C5H4(CH2)nPPh2(AuCl)}2].2THF n = 0 (1); n = 2 (2); n = 3 (3) and [TiCl2{η5-C5H4κ-(CH2)nPPh2}2(PtCl2)].2THF (M = Pd, n = 0 (4); n = 2 (5); n = 3 (6); M = Pt, n = 0 (7); n = 2 (8); n = 3 (9)) have been synthesized and characterized by different spectroscopic techniques and mass spectrometry. The molecular structures of compounds 1–9 have been investigated by means of density-functional calculations. The calculated IR spectra of the optimized structures fit well with the experimental IR data obtained for 1–9. The stability of the heterometallic compounds in deuterated solvents (CDCl3, d6-dmso, mixtures 50:50 d6-dmso/D2O, 1:99 d6-dmso/D2O at acidic pH and at neutral pH) has been evaluated by 31P and 1H NMR spectroscopy showing a higher stability for these compounds than for Cp2TiCl2 or precursors [Ti{η5-C5H4(CH2)nPPh2}2]. The new compounds display a lower acidity (1 to 2 units) than Cp2TiCl2. The decomposition products have been identified over time. Complexes 1–9 have been tested as potential anticancer agents and their cytotoxicity properties were evaluated in vitro against HeLa human cervical carcinoma and DU-145 human prostate cancer cells. TiAu2 and TiPd compounds were highly cytotoxic for these two cell lines. The interactions of the compounds with Calf Thymus DNA have been evaluated by Thermal Denaturation (1–9) and by Circular Dichroism (1, 3, 4, 7) spectroscopic methods. All these complexes show a stronger interaction with DNA than that displayed by Cp2TiCl2 at neutral pH. The data is consistent with electrostatic interactions with DNA for TiAu2 compounds and for a covalent binding mode for TiM (M = Pd, Pt) complexes.

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Section: Resultsmentioning

confidence: 99%

Titanocene–Phosphine Derivatives as Precursors to Cytotoxic Heterometallic TiAu₂and TiM (M = Pd, Pt) Compounds. Studies of Their Interactions with DNA

et al. 2011

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“…SA has been shown to bind hard metals such as Ti(IV) in metal-chelate form (13,20). Binding to SA affords a mechanism by which a Ti(IV) compound, such as the titanocene moiety (22,23), could be delivered intact to cancer cells and directly exhibit its effect. Several hydrolysis-prone Ti(IV) compounds, including the titanocene moiety, importantly, bind to SA (13,20,22,23).…”

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confidence: 99%

“…Binding to SA affords a mechanism by which a Ti(IV) compound, such as the titanocene moiety (22,23), could be delivered intact to cancer cells and directly exhibit its effect. Several hydrolysis-prone Ti(IV) compounds, including the titanocene moiety, importantly, bind to SA (13,20,22,23). However, similar to results with Tf, the addition of SA to cell-viability assays does not improve the cytotoxicity displayed by different Ti(IV) compounds (24), except Titanocene Y (24).…”

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confidence: 99%

Cytotoxicity of a Ti(IV) compound is independent of serum proteins

Tinoco

Thomas

Incarvito

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Titanium(IV) compounds are excellent anticancer drug candidates, but they have yet to find success in clinical applications. A major limitation in developing further compounds has been a general lack of understanding of the mechanism governing their bioactivity. To determine factors necessary for bioactivity, we tested the cytotoxicity of different ligand compounds in conjunction with speciation studies and mass spectrometry bioavailability measurements. These studies demonstrated that the Ti(IV) compound of N, N′-di(o-hydroxybenzyl)ethylenediamine-N,N′-diacetic acid (HBED) is cytotoxic to A549 lung cancer cells, unlike those of citrate and naphthalene-2,3-diolate. Although serum proteins are implicated in the activity of Ti(IV) compounds, we found that these interactions do not play a role in [TiO(HBED)] − activity. Subsequent compound characterization revealed ligand properties necessary for activity. These findings establish the importance of the ligand in the bioactivity of Ti(IV) compounds, provides insights for developing next-generation Ti(IV) anticancer compounds, and reveal [TiO (HBED)] − as a unique candidate anticancer compound.drug delivery | transferrin | albumin | metal-based anticancer compounds

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“…Proteins in general are flexible molecules that can accommodate ligands with vastly different shapes and sizes (Sarsama et al, 2011). Reports on electrochemical investigations have also shown that titanocene dichloride has higher affinity for proteins than for nucleic acids (Ravera et al, 2009). Minor structural modifications could have unpredictable effects on drug binding on the scaffolds.…”

Section: Discussionmentioning

confidence: 99%

Controlled release of titanocene into the hybrid nanofibrous scaffolds to prevent the proliferation of breast cancer cells

Laiva

Venugopal

Karuppuswamy

et al. 2015

International Journal of Pharmaceutics

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Electrochemical evaluation of the interaction between antitumoral titanocene dichloride and biomolecules

Cited by 23 publications

References 33 publications

Titanocene–Phosphine Derivatives as Precursors to Cytotoxic Heterometallic TiAu₂and TiM (M = Pd, Pt) Compounds. Studies of Their Interactions with DNA

Titanocene–Phosphine Derivatives as Precursors to Cytotoxic Heterometallic TiAu₂and TiM (M = Pd, Pt) Compounds. Studies of Their Interactions with DNA

Cytotoxicity of a Ti(IV) compound is independent of serum proteins

Controlled release of titanocene into the hybrid nanofibrous scaffolds to prevent the proliferation of breast cancer cells

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Electrochemical evaluation of the interaction between antitumoral titanocene dichloride and biomolecules

Cited by 23 publications

References 33 publications

Titanocene–Phosphine Derivatives as Precursors to Cytotoxic Heterometallic TiAu2and TiM (M = Pd, Pt) Compounds. Studies of Their Interactions with DNA

Titanocene–Phosphine Derivatives as Precursors to Cytotoxic Heterometallic TiAu2and TiM (M = Pd, Pt) Compounds. Studies of Their Interactions with DNA

Cytotoxicity of a Ti(IV) compound is independent of serum proteins

Controlled release of titanocene into the hybrid nanofibrous scaffolds to prevent the proliferation of breast cancer cells

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Titanocene–Phosphine Derivatives as Precursors to Cytotoxic Heterometallic TiAu₂and TiM (M = Pd, Pt) Compounds. Studies of Their Interactions with DNA

Titanocene–Phosphine Derivatives as Precursors to Cytotoxic Heterometallic TiAu₂and TiM (M = Pd, Pt) Compounds. Studies of Their Interactions with DNA