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Synthesis, structure and anticancer properties of new biotin- and morpholine-functionalized ruthenium and osmium half-sandwich complexes

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Abstract

Ruthenium (Ru) and osmium (Os) complexes are of sustained interest in cancer research and may be alternative to platinum-based therapy. We detail here three new series of ruthenium and osmium complexes, supported by physico-chemical characterizations, including time-dependent density functional theory, a combined experimental and computational study on the aquation reactions and the nature of the metal–arene bond. Cytotoxic profiles were then evaluated on several cancer cell lines although with limited success. Further investigations were, however, performed on the most active series using a genetic approach based on RNA interference and highlighted a potential multi-target mechanism of action through topoisomerase II, mitotic spindle, HDAC and DNMT inhibition.

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Crystal structures have been filed in the Cambridge Crystallographic Data Centre (CCDC). Deposit numbers: 2061654 for RuAEM and 2061655 for OsAEM.

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Acknowledgements

M.M. thanks Sabrina Cauchies for the ICP-MS experiments.

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Authors and Affiliations

  1. Microbiology, Bioorganic and Macromolecular Chemistry, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), 1050, Brussels, Belgium

    Mickaël Marloye, Michel Gelbcke, Franck Meyer, François Dufrasne & Gilles Berger

  2. Department of Biomedical Engineering, Pennsylvania State University, University Park, PA, USA

    Haider Inam, Connor J. Moore & Justin R. Pritchard

  3. Laboratoire G-Time, Université Libre de Bruxelles, 1050, Brussels, Belgium

    Vinciane Debaille

  4. Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Gilles Berger

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  1. Mickaël Marloye
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  2. Haider Inam
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  4. Vinciane Debaille
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  5. Justin R. Pritchard
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  9. Gilles Berger
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Contributions

MM and GB conceived and designed the research program. JRP, HI and CJM participated the shRNA experiments. The manuscript was written by MM and GB with contributions from all the authors. MM prepared all figures.

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Correspondence to Gilles Berger.

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Marloye, M., Inam, H., Moore, C.J. et al. Synthesis, structure and anticancer properties of new biotin- and morpholine-functionalized ruthenium and osmium half-sandwich complexes. J Biol Inorg Chem 26, 535–549 (2021). https://doi.org/10.1007/s00775-021-01873-9

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