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Dimethylamino-functionalised and N-heteroaryl-substituted titanocene anticancer drugs: synthesis and cytotoxicity studies

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Summary

From the carbolithiation of 6-N,N-dimethylamino fulvene (3a) and different lithiated N-heterocyclic compounds (N,N-dimethylaminomethylpyrrole, 1-methylimidazole and 2,4-[bis(N′,N′-dimethylaminomethyl)]-N-methyl pyrrole), the corresponding lithium cyclopentadienide intermediate (4a–c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl4 resulting in dimethylamino-functionalised titanocenes 5a–c. When these titanocenes were tested against LLC-PK cells, the IC50 values obtained were of 13, and 63 μM for titanocenes 5b and 5c, respectively. The most cytotoxic titanocene in this paper (5a) with an IC50 value of 6.8 μM is found to be almost as cytotoxic as cis-platin, which showed an IC50 value of 3.3 μM, when tested on the epithelial pig kidney LLC-PK cell line, and titanocene 5c is approximately 400 times better than titanocene dichloride itself.

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Scheme 1
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Acknowledgements

The authors thank Science Foundation Ireland (SFI), the Higher Education Authority (HEA), the Centre for Synthesis and Chemical Biology (CSCB) and COST D39 for funding.

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Authors and Affiliations

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

    Thomas Hickey, James Claffey, Eoin Fitzpatrick, Megan Hogan, Clara Pampillón & Matthias Tacke

Authors
  1. Thomas Hickey
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  2. James Claffey
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  3. Eoin Fitzpatrick
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  4. Megan Hogan
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  5. Clara Pampillón
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  6. Matthias Tacke
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Corresponding author

Correspondence to Matthias Tacke.

Appendix

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Supplementary Information

Table 2 DFT calculated structures and energies of 5c using B3LYP/6-31G**
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Hickey, T., Claffey, J., Fitzpatrick, E. et al. Dimethylamino-functionalised and N-heteroaryl-substituted titanocene anticancer drugs: synthesis and cytotoxicity studies. Invest New Drugs 25, 425–433 (2007). https://doi.org/10.1007/s10637-007-9061-8

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  • DOI: https://doi.org/10.1007/s10637-007-9061-8

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