Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications
By J. Zielonka, J. Joseph, A. Sikora, M. Hardy, O. Ouari, J. Vasquez-Vivar, Gang Cheng, Marcos López, B. Kalyanaraman. Chemical Reviews, 2017
1,341 citations recorded by the source corpus.
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 potentials of cell and mitochondrial membranes, 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.
Subfields: Clinical Biochemistry, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/10334f890f9e02c617dc23e2b02d5308b023df91
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
- Yajun Wang
- T. Gong
- Yongliang Cao
- Yongkai Cao
- Dahua Fan
- Meiqun Cao
Citations in the corpus
- Nanomedicine in cancer therapy (2023, background): “Triphenylphosphonium (TPP), a delocalized lipophilic cation that can efficiently accumulate in mitochondria through interactions with the negatively charged mitochondrial membrane, has also been frequently utilized as a targeting moiety to deliver various small molecules and nanoparticles to mitocho”