Design, synthesis, and some aspects of the biological activity of mitochondria-targeted antioxidants

Коршунова, Г. А.; Shishkina, A. V.; Скулачев, М. В.

doi:10.1134/s0006297917070021

Cited by 21 publications

(15 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Skulachev (SkQ1) antioxidants are similar to MitoQ, however they involve the use of conjugated mitochondrial targeted motifs, like rhodamine and TPP, to plastiquinone [171] .…”

Section: Toxin Induced Models Of Admentioning

confidence: 99%

Mitochondrial abnormalities in Parkinson's disease and Alzheimer's disease: can mitochondria be targeted therapeutically?

MacDonald

Barnes

Hastings

et al. 2018

Biochemical Society Transactions

164

106

View full text Add to dashboard Cite

Mitochondrial abnormalities have been identified as a central mechanism in multiple neurodegenerative diseases and, therefore, the mitochondria have been explored as a therapeutic target. This review will focus on the evidence for mitochondrial abnormalities in the two most common neurodegenerative diseases, Parkinson's disease and Alzheimer's disease. In addition, we discuss the main strategies which have been explored in these diseases to target the mitochondria for therapeutic purposes, focusing on mitochondrially targeted antioxidants, peptides, modulators of mitochondrial dynamics and phenotypic screening outcomes.

show abstract

“…Skulachev (SkQ1) antioxidants are similar to MitoQ, however they involve the use of conjugated mitochondrial targeted motifs, like rhodamine and TPP, to plastiquinone [171] .…”

Section: Toxin Induced Models Of Admentioning

confidence: 99%

Mitochondrial abnormalities in Parkinson's disease and Alzheimer's disease: can mitochondria be targeted therapeutically?

MacDonald

Barnes

Hastings

et al. 2018

Biochemical Society Transactions

164

106

View full text Add to dashboard Cite

show abstract

“…Previously, we have shown that plastoquinone as an antioxidative part of the conjugate demonstrates wide protective effects [ 16 ] and later it has been elucidated that neuroprotective properties of mitochondria-targeted antioxidants were determined not only by the quinone part but also the penetrating part itself [ 17 ]. Plastoquinone is present in natural photosynthetic systems, being an electron carrier in electron transport chains of chloroplasts and cyanobacteria reported to possess a strong antioxidative property [ 18 , 19 ]. The therapeutic efficiency of mitochondria-targeted antioxidants has been demonstrated in animal models of oxidative stress-related pathologies of brain [ 17 , 20 , 21 , 22 ], kidneys [ 22 , 23 , 24 , 25 , 26 ], and heart [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects of Mitochondria-Targeted Plastoquinone in a Rat Model of Neonatal Hypoxic–Ischemic Brain Injury

et al. 2018

View full text Add to dashboard Cite

Neonatal hypoxia–ischemia is one of the main causes of mortality and disability of newborns. To study the mechanisms of neonatal brain cell damage, we used a model of neonatal hypoxia–ischemia in seven-day-old rats, by annealing of the common carotid artery with subsequent hypoxia of 8% oxygen. We demonstrate that neonatal hypoxia–ischemia causes mitochondrial dysfunction associated with high production of reactive oxygen species, which leads to oxidative stress. Targeted delivery of antioxidants to the mitochondria can be an effective therapeutic approach to treat the deleterious effects of brain hypoxia–ischemia. We explored the neuroprotective properties of the mitochondria-targeted antioxidant SkQR1, which is the conjugate of a plant plastoquinone and a penetrating cation, rhodamine 19. Being introduced before or immediately after hypoxia–ischemia, SkQR1 affords neuroprotection as judged by the diminished brain damage and recovery of long-term neurological functions. Using vital sections of the brain, SkQR1 has been shown to reduce the development of oxidative stress. Thus, the mitochondrial-targeted antioxidant derived from plant plastoquinone can effectively protect the brain of newborns both in pre-ischemic and post-stroke conditions, making it a promising candidate for further clinical studies.

show abstract

“…It was shown that the new cationic uncoupler—rhodamine-19 butyl ether (C4R1) effectively accumulates in mitochondria to a certain concentration, without disturbing their vital functions. In experiments on rats—models of ischemic stroke, it was shown that the introduction of C4R1 after a reversible violation of cerebral circulation significantly reduced the scale of brain damage to animals and related neurological disorders (Korshunova et al, 2017; Lyamzaev et al, 2018; Silachev et al, 2018; Genrikhs et al, 2019). It should be noted that preventing the production of oxygen radicals in mitochondria is a fundamental principle in the fight against many diseases.…”

Section: Discussionmentioning

confidence: 99%

Cytoprotective Effects of Dinitrosyl Iron Complexes on Viability of Human Fibroblasts and Cardiomyocytes

et al. 2019

View full text Add to dashboard Cite

Nitric oxide (NO) is an important signaling molecule that plays a key role in maintaining vascular homeostasis. Dinitrosyl iron complexes (DNICs) generating NO are widely used to treat cardiovascular diseases. However, the involvement of DNICs in the metabolic processes of the cell, their protective properties in doxorubicin-induced toxicity remain to be clarified. Here, we found that novel class of mononuclear DNICs with functional sulfur-containing ligands enhanced the cell viability of human lung fibroblasts and rat cardiomyocytes. Moreover, DNICs demonstrated remarkable protection against doxorubicin-induced toxicity in fibroblasts and in rat cardiomyocytes (H9c2 cells). Data revealed that the DNICs compounds modulate the mitochondria function by decreasing the mitochondrial membrane potential (ΔΨm). Results of flow cytometry showed that DNICs were not affected the proliferation, growth of fibroblasts. In addition, this study showed that DNICs did not affect glutathione levels and the formation of reactive oxygen species in cells. Moreover, results indicated that DNICs maintained the ATP equilibrium in cells. Taken together, these findings show that DNICs have protective properties in vitro. It was further suggested that DNICs may be uncouplers of oxidative phosphorylation in mitochondria and protective mechanism is mainly provided by the leakage of excess charge through the mitochondrial membrane. It is assumed that the DNICs have the therapeutic potential for treating cardiovascular diseases and for decreasing of chemotherapy-induced cardiotoxicity in cancer survivors.

show abstract

Design, synthesis, and some aspects of the biological activity of mitochondria-targeted antioxidants

Cited by 21 publications

References 59 publications

Mitochondrial abnormalities in Parkinson's disease and Alzheimer's disease: can mitochondria be targeted therapeutically?

Mitochondrial abnormalities in Parkinson's disease and Alzheimer's disease: can mitochondria be targeted therapeutically?

Neuroprotective Effects of Mitochondria-Targeted Plastoquinone in a Rat Model of Neonatal Hypoxic–Ischemic Brain Injury

Cytoprotective Effects of Dinitrosyl Iron Complexes on Viability of Human Fibroblasts and Cardiomyocytes

Contact Info

Product

Resources

About