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Proliferative and antiproliferative effects in substituted titanocene anticancer drugs

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Abstract

Substituted titanocenes like ansa-titanocenes, diarylmethyl-substituted and benzyl-substituted titanocenes, are known for their cytotoxic potential and they can be synthesised using 6-arylfulvenes. Nevertheless, in the case of using 6-(4-morpholin-4yl-phenyl) fulvene (5a) or 6-{[bis-(2-methoxyethyl)amino]phenyl} fulvene (5b) the synthetic possibilities seem to be limited, but the morpholino and the bis-(2-methoxyethyl)amino substituent are in terms of an improved water solubility and drug availability in the cell very interesting groups. The corresponding benzaldehydes, which are the starting material for the synthesis of these fulvenes, were not commercially available and therefore, a modified synthetic approach had to be introduced. Nevertheless, the reactivity of the obtained fulvenes was unexpected and only the ansa-titanocene bis-[{[bis-(2-methoxyethyl)amino]phenyl}cyclopentadienyl] titanium(IV) dichloride (6b) and the benzyl-substituted titanocene [1,2-di(cyclopentadienyl)-1,2-di(4-morpholin-4yl-phenyl)-ethanediyl] titanium dichloride (8a) could be obtained and characterised.

When the benzyl-substituted titanocene (8a) was tested against pig kidney cells (LLC-PK) an anti-proliferative effect, resulting in an IC50 value of 25 µM, was observed. This IC50 value is in the lower range of the cytotoxicities evaluated for titanocenes up to now. The ansa-titanocene (6b) showed surprisingly, when tested on the same cell line, a proliferative effect.

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Authors and Affiliations

  1. UCD School of Chemistry and Chemical Biology, Conway Institute of Biomolecular and Biomedical Research, Centre for Synthesis and Chemical Biology (CSCB), University College Dublin, Belfield, Dublin 4, Ireland

    Katja Strohfeldt, Helge Müller-Bunz, Clara Pampillón & Matthias Tacke

Authors
  1. Katja Strohfeldt
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  2. Helge Müller-Bunz
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  3. Clara Pampillón
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  4. Matthias Tacke
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Correspondence to Matthias Tacke.

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Strohfeldt, K., Müller-Bunz, H., Pampillón, C. et al. Proliferative and antiproliferative effects in substituted titanocene anticancer drugs. Transition Met Chem 32, 971–980 (2007). https://doi.org/10.1007/s11243-007-0265-8

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  • DOI: https://doi.org/10.1007/s11243-007-0265-8

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