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Piperazine derivatives as iron chelators: a potential application in neurobiology

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Abstract

Polysubstituted piperazine derivatives, designed as new iron chelators, were synthesized and fully characterized by nuclear magnetic resonance and mass spectroscopy. Their potential to prevent iron-induced neurotoxicity was assessed using a cellular model of Parkinson disease. We demonstrated their ability to provide sustained neuroprotection to dopaminergic neurons that are vulnerable in this pathology. The iron chelating properties of the new compounds were determined by spectrophotometric titration illustrating that high affinity for iron is not associated with important neuroprotective effects.

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Acknowledgments

This work was supported by a Ph.D. Grant from the University Paris Diderot (S. Abdelsayed). The National Center for Scientific Research and the University Paris Diderot are thanked for financial support. The research leading to these results received funding from the program “Investissements d’avenir” ANR-10-IAIHU-06.The authors also thank Chang-Zhi Dong for his help with HPLC experiments, John S. Lomas for carefully reading the manuscript, and the Small Molecule Mass Spectrometry platform of IMAGIF (Centre de Recherche de Gif—www.imagif.cnrs.fr) for facilities and expertise.

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Authors and Affiliations

  1. Univ Paris Diderot, Sorbonne Paris Cité, ITODYS, UMR 7086, CNRS, 15 rue Jean-Antoine de Baïf, 75205, Paris Cedex 13, France

    S. Abdelsayed, N. T. Ha Duong, J. M. El Hage Chahine & N. Serradji

  2. Inserm, U 1127, 75013, Paris, France

    C. Bureau, P. P. Michel & E. C. Hirsch

  3. CNRS, UMR 7225, 75013, Paris, France

    C. Bureau, P. P. Michel & E. C. Hirsch

  4. Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, 75013, Paris, France

    C. Bureau, P. P. Michel & E. C. Hirsch

  5. Institut du Cerveau et de la Moelle épinière, ICM, 75013, Paris, France

    C. Bureau, P. P. Michel & E. C. Hirsch

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  1. S. Abdelsayed
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  2. N. T. Ha Duong
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  3. C. Bureau
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  4. P. P. Michel
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  5. E. C. Hirsch
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  6. J. M. El Hage Chahine
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  7. N. Serradji
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Correspondence to J. M. El Hage Chahine or N. Serradji.

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Abdelsayed, S., Ha Duong, N.T., Bureau, C. et al. Piperazine derivatives as iron chelators: a potential application in neurobiology. Biometals 28, 1043–1061 (2015). https://doi.org/10.1007/s10534-015-9889-x

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  • DOI: https://doi.org/10.1007/s10534-015-9889-x

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