Abstract
Cell-impermeant iron chelator desferrioxamine (DFO) can have access to organelles if appended to suitable vectors. Mitochondria are important targets for the treatment of iron overload-related neurodegenerative diseases. Triphenylphosphonium (TPP) is a delocalized lipophilic cation used to ferry molecules to mitochondria. Here we report the synthesis and characterization of the conjugate TPP–DFO as a mitochondrial iron chelator. TPP–DFO maintained both a high affinity for iron and the antioxidant activity when compared to parent DFO. TPP–DFO was less toxic than TPP alone to A2780 cells (IC50 = 135.60 ± 1.08 and 4.34 ± 1.06 μmol L−1, respectively) and its native fluorescence was used to assess its mitochondrial localization (Rr = +0.56). These results suggest that TPP–DFO could be an interesting alternative for the treatment of mitochondrial iron overload e.g. in Friedreich’s ataxia.
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Acknowledgements
This work was supported by CAPES, FAPESP and CNPq (Brazilian government agencies). The authors thank Dr. Cleber Wanderlei Liria for discussions and technical assistance.
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Alta, R.Y.P., Vitorino, H.A., Goswami, D. et al. Triphenylphosphonium-desferrioxamine as a candidate mitochondrial iron chelator. Biometals 30, 709–718 (2017). https://doi.org/10.1007/s10534-017-0039-5
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DOI: https://doi.org/10.1007/s10534-017-0039-5