gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

Novel Titanocene Anti-Cancer Drugs

Meeting Abstract

  • corresponding author presenting/speaker Matthias Tacke - The UCD School of Chemistry and Chemical Biology, Dublin, Ireland,
  • Katja Strohfeldt - The UCD School of Chemistry and Chemical Biology, Dublin, Ireland
  • Clara Pampillón - The UCD School of Chemistry and Chemical Biology, Dublin, Ireland
  • Nigel Sweeney - The UCD School of Chemistry and Chemical Biology, Dublin, Ireland

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocOP431

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dkk2006/06dkk541.shtml

Veröffentlicht: 20. März 2006

© 2006 Tacke et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Titanocene dichloride (Cp2TiCl2) shows significant activity against a variety of human cancer cell lines, overcomes the resistance against cis-platin and reached two clinical Phase II studies against renal cell and metastatic breast cancer. But Cp2TiCl2 failed in these studies due to a lack in anti-proliferative activity and also demonstrated severe renal and liver toxicities at high concentrations.

The aim of our research is to synthesise suitably substituted titanocenes and ansa-titanocenes in order to control the physiological uptake of the titanocenes and to overcome the toxicity effects exhibited by titanocene dichloride. In addition we model the titanocene-DNA interaction leading finally to apoptosis.

Ansa-titanocene dichlorides are obtained by reductive dimerisation of substituted aryl fulvenes with TiCl2, while un-bridged titanocenes are available from fulvenes through the addition of lithium hydride or aryl lithium ([1], [2], [3], [4], [5]).

We investigate the cytotoxic activity of all titanocenes on LLC-PK pig kidney carcinoma cells and that of selected titanocenes on a 36 cell-line panel in vitro. Results show that our most effective titanocene has a significantly higher activity than Cp2TiCl2 itself. Recently, our best titanocenes have successfully finished pre-clinical animal studies (EAT and Caki-1 in mice) as well as clinical ex vivo tests involving a variety of explanted human tumours.

Acknowledgement: The authors want to acknowledge financial support from COST, HEA and SFI.


References

1.
Tacke M, Allen LT, Cuffe LP, Gallagher WM, Lou Y, Mendoza O, Müller-Bunz H, Rehmann FJK, Sweeney N. J Organomet Chem. 2004; 689:2242-9.
2.
Tacke M, Cuffe LP, Gallagher WM, Lou Y, Mendoza O, Müller-Bunz H,  Rehmann FJK, Sweeney N. J Inorg Biochem. 2004;98:1987-94.
3.
Rehmann FJK, Cuffe LP, Mendoza O, Rai DK, Sweeney N, Strohfeldt K, Gallagher WM, Tacke M. Appl Organomet Chem. 2005;19:293-300.
4.
Rehmann FJK, Rous AJ, Mendoza O, Sweeney NJ, Strohfeldt K, Gallagher WM, Tacke M. Polyhedron. 2005; 24:1250-5.
5.
Sweeney N, Mendoza O, Müller-Bunz H, Pampillón C, Rehmann FJK, Strohfeldt K, Tacke M. J Organomet Chem. 2005; 690:4537-44.