Mitoquinol Mesylate
| MitoQ Structural Formula | |
| Names | |
|---|---|
| IUPAC name
Phosphonium, [10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien- 1-yl)decyl]triphenyl-, methanesulfonate
| |
| Other names
mitoquinone mesylate, MitoQ10, mitoubiquinone mesylate
| |
| Identifiers | |
3D model (JSmol)
|
|
| ChemSpider | |
| ECHA InfoCard | Lua error in Module:Wikidata at line 879: attempt to index field 'wikibase' (a nil value). Lua error in Module:Wikidata at line 879: attempt to index field 'wikibase' (a nil value). |
| E number | Lua error in Module:Wikidata at line 879: attempt to index field 'wikibase' (a nil value). |
PubChem CID
|
|
| UNII | |
CompTox Dashboard (EPA)
|
|
| |
| |
| Properties | |
| C38H47O7PS | |
| Molar mass | 678.82 g·mol−1 |
| Appearance | Viscous orange syrup |
| Solubility | dichloromethane, ethanol, methanol, chloroform, water(Insoluble in hexane, ether |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
| Infobox references | |
Mitoquinol mesylate (MitoQ10) is a mitochondria-targeted antioxidant designed to accumulate within mitochondria to help protect against oxidative damage.[1][2][3] Mitoquinol mesylate has the same identical active component as CoQ10 (Ubiquinone).[1]
Design and synthesis
Mitoquinol mesylate was synthesized in the late 1990s by Michael P. Murphy and Robin A.J. Smith.[2] Both Murphy and Smith were at the University of Otago, Dunedin, New Zealand where Murphy was a mitochondrial biochemist in the Department of Biochemistry and Smith was an organic chemist at the Department of Chemistry.[2] The molecule was made by Geoffery Kelso, a PhD student present in Smith's lab.[2]
Properties
Mitoquinol mesylate accumulates within the mitochondria in vivo increasing antioxidant capacity and decreasing mitochondrial oxidative damage.[4] This was achieved by incorporating a positively charged lipophilic cation onto the active ubiquinone.[5] The lipophilic cation used is based on the triphenylphosphonium structure, which is known to accumulate within the negative mitochondrial matrix.[5][6] In the solid form, the positive charge of mitoquinol mesylate is normally neutralized by mesylate, a negatively charged anion forming a salt.[5] Mitoquinol mesylate is present in two different forms, the oxidised mitoQuinone and the reduced mitoQuinol which is the active antioxidant.[5]
The alkyl chain connecting the lipophilic triphenylphosphonium cation to the ubiquinol is 10 carbons in length[7][8]. The benefit of having a 10 carbon chain was that the increased hydrophobicity increased the uptake of mitoquinol mesylate into the mitochondria and also the ability to access the active site of Complex II so it can be converted to the active form unlike shorter carbon chain lengths.[6][7][8] These properties lead to mitoquinol mesylate being mainly (>90%) adsorbed to the matrix-facing surface of the inner membrane, where the lipophilic triphenylphosphonium cation sits on the surface of the membrane while the ubiquinol antioxidant penetrates into the membrane core.[6][8] The ubiquinol that penetrates into the mitochondrial inner membrane can donate a hydrogen atom to reactive oxygen species formed during lipid peroxidation blocking this form of oxidative damage.[9]
Human Clinical Testing
The first of two-Phase II clinical trials established the safety and efficacy on Parkinson’s disease and hepatitis C.[1][2] These studies showed that mitoquinol mesylate was safe to target mitochondria in humans long term.[1][2]
In a 6-week clinical trial of healthy patients aged between 60-79 with impaired endothelial function using 20mg/day, mitoquinol mesylate was well tolerated and improved flow-mediated dilation by 42%.[2]
References
- ↑ 1.0 1.1 1.2 1.3 Battogtokh, Gantumur; Choi, Yeon Su; Kang, Dong Seop; Park, Sang Jun; Shim, Min Suk; Huh, Kang Moo; Cho, Yong-Yeon; Lee, Joo Young; Lee, Hye Suk (2018). "Mitochondria-targeting drug conjugates for cytotoxic, anti-oxidizing and sensing purposes: current strategies and future perspectives". Acta Pharmaceutica Sinica B. 8 (6): 862–880. doi:10.1016/j.apsb.2018.05.006. ISSN 2211-3835. PMC 6251809. PMID 30505656.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Agrwal, A; Mabalirajan, U (2016). "Rejuvenating cellular respiration for optimizing respiratory function: targeting mitochondria". Am J Physiol Lung Cell Mol Physiol. 310 (2): L103–13. doi:10.1152/ajplung.00320.2015. PMID 26566906.
- ↑ Li, Huige; Horke, Sven; Forstermann, Ulrich (2013). "Oxidative Stress in Vascular Disease and its Pharmacological Prevention". Trends in Pharmacological Sciences. 34 (6): 313–319. doi:10.1016/j.tips.2013.03.007. ISSN 1873-4596. PMID 23608227.
- ↑ Skulachev, Vladimir P.; Anisimov, Vladimir N.; Antonenko, Yuri N.; Bakeeva, Lora E.; Chernyak, Boris V.; Erichev, Valery P.; Filenko, Oleg F.; Kalinina, Natalya I.; Kapelko, Valery I. (2009). "An Attempt to Prevent Senescence: A Mitochondrial Approach". Biochimica et Biophysica Acta (BBA)-Bioenergetics. 1787 (5): 437–461. doi:10.1016/j.bbabio.2008.12.008. PMID 19159610.
- ↑ 5.0 5.1 5.2 5.3 Hoye, Adam T.; Davoren, Jennifer E.; Wipf, Peter; Fink, Mitchell P.; Kagan, Valerian E. (2008). "Targeting Mitochondria". Accounts of Chemical Research. 40 (1): 87–97. doi:10.1021/ar700135m. PMID 18193822.
- ↑ 6.0 6.1 6.2 Zielonka, Jacek; Joseph, Joy; Sikora, Adam; Hardy, Micael; Ouari, Olivier; Vasquez-Vivar, Jeannette; Cheng, Gang; Lopez, Marcos; Kalyanaraman, Balaraman (2017). "Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications". Chemical Reviews. 117 (15): 10043–10120. doi:10.1021/acs.chemrev.7b00042. ISSN 0009-2665. PMC 5611849. PMID 28654243.
- ↑ 7.0 7.1 Gruber, Jan; Fong, Sheng; Chen, Ce-Belle; Yoong, Sialee; Pastorin, Giorgia; Schaffer, Sebastian; Cheah, Irwin; Halliwell, Barry (2013). "Mitochondria-targeted antioxidants and metabolic modulators as pharmacological interventions to slow ageing". Biotechnology Advances. 31 (5): 563–592. doi:10.1016/j.biotechadv.2012.09.005. ISSN 0734-9750. PMID 23022622.
- ↑ 8.0 8.1 8.2 Zielonka, J; Sikora, Adam; Hardy, Micael; Ouari, Olivier; Vasquez-Vivar, Jeannette; Cheng, Gang; Lopez, Marcos; Kalyanaraman, Balaraman (2017). "Mitochondria-targeted Triphenylphosphonium-based Compounds: Syntheses, Mechanisms of Action and Therapeutic and Diagnostic Applciations". Chem Rev. 117 (15): 10043–10120. doi:10.1021/acs.chemrev.7b00042. PMC 5611849. PMID 28654243.
- ↑ Apostolova, Nadezda; Victor, Victor M (2015). "Molecular Strategies For Targeting Antioxidants to Mitochondria: Therapeutic Implications". Antioxidants & Redox Signaling. 22 (8): 686–729. doi:10.1089/ars.2014.5952. PMC 4350006. PMID 25546574.
This article "Mitoquinol Mesylate" is from Wikipedia. The list of its authors can be seen in its historical and/or the page Edithistory:Mitoquinol Mesylate. Articles copied from Draft Namespace on Wikipedia could be seen on the Draft Namespace of Wikipedia and not main one.
