Synthesis of triphenylphosphonium vitamin E derivatives as mitochondria-targeted antioxidants

Jameson, Victoria J.A.; Cochemé, Helena M.; Logan, Angela; Hanton, Lyall R.; Smith, Robin A.J.; Murphy, Michael P.

doi:10.1016/j.tet.2015.09.014

Cited by 34 publications

(29 citation statements)

References 50 publications

(54 reference statements)

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“…It is beneficial against oxidative stress in both cells and animals, but has far lower antioxidant activity than MitoVitE in standard in vitro rat brain homogenate lipid peroxidation assays. 27 In DRG cells in vitro, we found that MitoVitE, but not Trolox, protected against mitochondrial dysfunction induced by paclitaxel.…”

Section: Discussionmentioning

confidence: 73%

MitoVitE, a mitochondria-targeted antioxidant, limits paclitaxel-induced oxidative stress and mitochondrial damage in vitro, and paclitaxel-induced mechanical hypersensitivity in a rat pain model

McCormick

Lowes

Colvin

et al. 2016

British Journal of Anaesthesia

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Paclitaxel affected mitochondrial function and glutathione in DRG cells, which was abrogated by MitoVitE but not Trolox, without decreasing cancer cell cytotoxicity. In rats, paclitaxel-induced mechanical hypersensitivity was ameliorated by MitoVitE treatment to an extent similar to duloxetine. These data confirm mitochondria as a mechanistic target for paclitaxel-induced damage and suggest mitochondria targeted antioxidants as future therapeutic strategies.

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Section: Discussionmentioning

confidence: 73%

MitoVitE, a mitochondria-targeted antioxidant, limits paclitaxel-induced oxidative stress and mitochondrial damage in vitro, and paclitaxel-induced mechanical hypersensitivity in a rat pain model

McCormick

Lowes

Colvin

et al. 2016

British Journal of Anaesthesia

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“…Recently, a new general synthetic pathway to MitoVit E homologs, which have alkyl chain lengths ranging from 2 to 11 carbon atoms, was reported. 434 In the cell-free system, MitoVit 2 E and MitoVit 10 E showed similar protective effects against lipid peroxidation in rat liver mitochondria, significantly stronger than the “untargeted” chromanol analog. α-tocopheryl succinate (VES) was also delivered to mitochondria using TPP + -tagged nanoparticles as a vehicle.…”

Section: Mitochondria-targeted Bioactive Compounds As Potential Thmentioning

confidence: 92%

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

Zielonka¹,

Joseph²,

et al. 2017

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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.

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“…It would therefore be desirable to know the time-course of oxidant production in a disease model so that initiation of direct antioxidant therapy can be optimally timed. Precursors of endogenous antioxidants, such glutathione (GSH) can be achieved by N-acetyl cysteine (NAC) which is approved for human use in acetaminophen toxicity but shows promise in many neurological diseases such as schizophrenia, HD and PD [40, 41]. …”

Section: Antioxidant Classesmentioning

confidence: 99%

Targeting Oxidative Stress in Central Nervous System Disorders

Patel

2016

Trends in Pharmacological Sciences

239

141

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There is widespread recognition that reactive oxygen species (ROS) play key roles in normal brain function and pathology in the context of neurological disease. Oxidative stress continues to remain a key therapeutic target for neurological diseases. In developing antioxidant therapies for neurological disease, special attention should be given to the brain’s unique vulnerability to oxidative insults and its architecture. Consideration of antioxidant therapy should be guided by a strong rationale for oxidative stress in the neurological disease. This review provides an overview of processes that can guide the development of antioxidant therapies in neurological diseases such as knowledge of basic redox mechanisms, unique features of brain pathophysiology, mechanisms and classes of antioxidants and desirable properties of drug candidates.

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Synthesis of triphenylphosphonium vitamin E derivatives as mitochondria-targeted antioxidants

Cited by 34 publications

References 50 publications

MitoVitE, a mitochondria-targeted antioxidant, limits paclitaxel-induced oxidative stress and mitochondrial damage in vitro, and paclitaxel-induced mechanical hypersensitivity in a rat pain model

MitoVitE, a mitochondria-targeted antioxidant, limits paclitaxel-induced oxidative stress and mitochondrial damage in vitro, and paclitaxel-induced mechanical hypersensitivity in a rat pain model

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

Targeting Oxidative Stress in Central Nervous System Disorders

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