Proliferative and anti-proliferative effects of titanium- and iron-based metallocene anti-cancer drugs

Vessières, Anne; Plamont, Marie‐Aude; Cabestaing, Claude; Claffey, James; Dieckmann, Sandra; Hogan, Megan; Müller‐Bunz, Helge; Strohfeldt, Katja; Tacke, Matthias

doi:10.1016/j.jorganchem.2008.11.071

Cited by 43 publications

(35 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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). Clearly, other factors are involved in the transport of, and activity exhibited by, cytotoxic Ti(IV) compounds.…”

mentioning

confidence: 66%

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

Tinoco

Thomas

Incarvito

et al. 2012

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

View full text Add to dashboard Cite

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

show abstract

mentioning

confidence: 66%

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

Tinoco

Thomas

Incarvito

et al. 2012

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

View full text Add to dashboard Cite

show abstract

“…As an alternative to transferrin involvement for titanium delivery into cells the involvement of the ubiquitous blood protein serum albumin (SA) has been suggested as a delivery mechanism for titanocenes. 7,8 Serum albumin receptors are overly represented on cancer cells and simple molecular modelling indicated a potential titanocene binding site (albeit with the chlorides not dissociated).…”

Section: Early Titanium Anti-cancer 'Mode(s) Of Action' Suggestionsmentioning

confidence: 99%

“…5'-dGMP) at pH 7.0-7.4 indicate no binding, just independent hydrolysis of 1 in these freshly prepared samples (NMR data at 0-20 h). 7 The type of cell death induced by 1 or other titanium-anticancer agents can also be a hallmark of its mode of action, so these are now briefly overviewed (Figure 3). Depending on the external stimuli provided to the cell (by the anti-cancer, or indeed any other agent) three major forms of programmed cell death (PCD) can occur: apoptosis (type 1), autophagy (type 2) or regulated necrosis (type 3).…”

Section: Early Titanium Anti-cancer 'Mode(s) Of Action' Suggestionsmentioning

confidence: 99%

“…The chiral 'salan-based' complexes of Tshuva and Manna show equally intriguing behaviour. 29 The separate enantiomers of (7) Figure 7), or even trimeric species, that are the putative active anti-cancer agents have been suggested to account for the behaviour of (7)(8). Fitting this picture those 'salan-based' complexes that are the most hydrolytically stable often exert the poorest biological performance.…”

Section: Recent Findings In Titanium Anti-cancer 'Mode(s) Of Action'mentioning

confidence: 99%

See 1 more Smart Citation

Using titanium complexes to defeat cancer: the view from the shoulders of titans

2017

View full text Add to dashboard Cite

When the first titanium complex with anticancer activity was identified in the 1970s, it was attractive, based on the presence of the dichloride unit in TiCl 2 Cp 2 (Cp = η-C 5 H 5 ) 2 , to assume its mode of biological action was closely aligned with cisplatin [cis-PtCl 2 (NH 3 ) 2 ]. Over the intervening 40 years however a far more complicated picture has arisen indicating multiple cellular mechanisms of cellular action can be triggered by titanium anti-cancer agents. This tutorial review aims to unpick the historical data and provide new researchers, without an explicit cancer biology background, a contemporary interpretation of both older and newer literature and to review the best techniques for attaining the identities of the biologically active titanium species and how these interact with the cancer cellular machinery. Key learning points(1) Understanding the problems in defining 'modes of action' in order to effectively design small molecular titanium-based therapeutic, agents when moving beyond simple 'structure vs. activity' correlations. (2) The dangers of over generalisation in historical 'mode of action' proposals in the absence of rigorous control experiments leading to proposals not fully in line with all (especially later) observations. (3) Titanium induced cellular morphology changes and contemporary thoughts on mode(s) of actionpresented in a way chemical scientists can 'get to grips with them' -understanding the hall marks of cellular death modes induced by titanium anti-cancer agents. (4) Modern tools for probing Ti-drug mechanisms of action, including: chiral probe complexes, added external proteins (transferrin, serum albumin); titanium solution speciation, and an overview of contemporary chemical-biology techniques of relevance to discovery of 'modes/mechanisms of action'.

show abstract

“…However, the reactions require high temperature and basic conditions and are therefore not compatible with biological environments. 64 The activity of water-soluble cyclopentadienyl complexes with phenanthroline or its 5-substituted analogues as chelating ligands follow the order [83][84][85][86] Interestingly, the vanadium and tin analogues of Titanocene Y are even more active towards cancer cells in vitro ( Figure 10). Bimetallic titanium-ruthenium complexes of the general formula [(η 5 -C 5 H 5 )(μ- Figure 12), consisting of a titanocene-dichloride component and a ruthenium-arene fragment, are markedly more active than their Ti or Ru monometallic components.…”

Section: Figurementioning

confidence: 99%