title: In search of novel highly active mitochondria-targeted antioxidants: thymoquinone and its cationic derivatives.
abstract: 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 H2O2-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.
authors.affiliation: Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Institute of Mitoengineering, Vorobyevy Gory 1, Moscow 119992, Russia.
authors.forename: Inna I
authors.initials: II
authors.lastname: Severina
authors.forename: Fedor F
authors.initials: FF
authors.lastname: Severin
authors.forename: Galina A
authors.initials: GA
authors.lastname: Korshunova
authors.forename: Natalya V
authors.initials: NV
authors.lastname: Sumbatyan
authors.forename: Tatyana M
authors.initials: TM
authors.lastname: Ilyasova
authors.forename: Ruben A
authors.initials: RA
authors.lastname: Simonyan
authors.forename: Anton G
authors.initials: AG
authors.lastname: Rogov
authors.forename: Tatyana A
authors.initials: TA
authors.lastname: Trendeleva
authors.forename: Renata A
authors.initials: RA
authors.lastname: Zvyagilskaya
authors.forename: Vera B
authors.initials: VB
authors.lastname: Dugina
authors.forename: Lidia V
authors.initials: LV
authors.lastname: Domnina
authors.forename: Elena K
authors.initials: EK
authors.lastname: Fetisova
authors.forename: Konstantin G
authors.initials: KG
authors.lastname: Lyamzaev
authors.forename: Mikhail Yu
authors.initials: MY
authors.lastname: Vyssokikh
authors.forename: Boris V
authors.initials: BV
authors.lastname: Chernyak
authors.forename: Maxim V
authors.initials: MV
authors.lastname: Skulachev
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Skulachev
authors.forename: Viktor A
authors.initials: VA
authors.lastname: Sadovnichii
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D016227:Benzoquinones / Q000378:metabolism / Q000494:pharmacology; D002412:Cations; D002463:Cell Membrane Permeability; D016503:Drug Delivery Systems; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010971:Plastoquinone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016227:Benzoquinones; D002412:Cations; D017382:Reactive Oxygen Species; C003466:thymoquinone; D010971:Plastoquinone