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In search of novel highly active mitochondria‐targeted antioxidants: Thymoquinone and its cationic derivatives
Author(s) -
Severina Inna I.,
Severin Fedor F.,
Korshunova Galina A.,
Sumbatyan Natalya V.,
Ilyasova Tatyana M.,
Simonyan Ruben A.,
Rogov Anton G.,
Trendeleva Tatyana A.,
Zvyagilskaya Renata A.,
Dugina Vera B.,
Domnina Lidia V.,
Fetisova Elena K.,
Lyamzaev Konstantin G.,
Vyssokikh Mikhail Yu,
Chernyak Boris V.,
Skulachev Maxim V.,
Skulachev Vladimir P.,
Sadovnichii Viktor A.
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.04.043
Subject(s) - thymoquinone , plastoquinone , chemistry , antioxidant , cationic polymerization , mitochondrion , respiratory chain , biochemistry , organic chemistry , chloroplast , thylakoid , gene
Since the times of the Bible, an extract of black cumin seeds was used as a medicine to treat many human pathologies. Thymoquinone (2‐demethylplastoquinone derivative) was identified as an active antioxidant component of this extract. Recently, it was shown that conjugates of plastoquinone and penetrating cations are potent mitochondria‐targeted antioxidants effective in treating a large number of age‐related pathologies. This review summarizes new data on the antioxidant and some other properties of membrane‐penetrating cationic compounds where 2‐demethylplastoquinone substitutes for plastoquinone. It was found that such a substitution significantly increases a window between anti‐ and prooxidant concentrations of the conjugates. Like the original plastoquinone derivatives, the novel compounds are easily reduced by the respiratory chain, penetrate through model and natural membranes, specifically accumulate in mitochondria in an electrophoretic fashion, and strongly inhibit H 2 O 2 ‐induced apoptosis at pico‐ and nanomolar concentrations in cell cultures. At present, cationic demethylplastoquinone derivatives appear to be the most promising mitochondria‐targeted drugs of the quinone series.