Skip to Main content Skip to Navigation
Journal articles

Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications

Abstract : Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases. Currently, the most effective way to deliver drugs specifically to mitochondria is by covalent linking a lipophilic cation such as an alkyltriphenylphosphonium moiety to a pharmacophore of interest. Other delocalized lipophilic cations, such as rhodamine, natural and synthetic mitochondria-targeting peptides, and nanoparticle vehicles, have, also been used for mitochondrial delivery of small molecules. Depending on the approach used, and the cell and mitochondrial membrane potentials, more than 1000-fold higher mitochondrial concentration can be achieved. Mitochondrial targeting has been developed to study mitochondrial physiology and dysfunction and the interaction between mitochondria and other subcellular organelles and for treatment of a variety of diseases such as neurodegeneration and cancer. In this Review, we discuss efforts to target small-molecule compounds to mitochondria for probing mitochondria function, as. diagnostic tools and potential therapeutics. We describe the physicochemical basis for mitochondrial accumulation of lipophilic cations, synthetic chemistry strategies to target compounds to mitochondria, mitochondrial probes, and sensors, and examples of mitochondrial targeting of bioactive compounds. Finally, we review published attempts to apply mitochondria-targeted agents for the treatment of cancer and neurodegenerative diseases.
Document type :
Journal articles
Complete list of metadatas

https://hal-amu.archives-ouvertes.fr/hal-01774202
Contributor : Marlene Delhaye <>
Submitted on : Monday, April 23, 2018 - 2:42:22 PM
Last modification on : Tuesday, April 24, 2018 - 1:30:50 AM

Links full text

Identifiers

Collections

Citation

Jacek Zielonka, Joy Joseph, Adam Sikora, Micael Hardy, Olivier Ouari, et al.. Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications. Chemical Reviews, American Chemical Society, 2017, 117 (15), pp.10043--10120. ⟨10.1021/acs.chemrev.7b00042⟩. ⟨hal-01774202⟩

Share

Metrics

Record views

120