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• W3149487008 abstract "The paper examines the molecular mechanisms of the cytotoxicity of conjugates of betulinic acid with the penetrating cation F16. The in vitro experiments on rat thymocytes revealed that all the obtained F16-betulinic acid derivatives showed more than 10-fold higher cytotoxicity as compared to betulinic acid and F16. In this case, 0.5–1 μM of all conjugates showed mitochondria-targeted action, inducing superoxide overproduction and reducing the mitochondrial potential of cells. Experiments on isolated rat liver mitochondria revealed the ability of conjugates to dose-dependently reduce the membrane potential of organelles, as well as the intensity of respiration and oxidative phosphorylation, which is also accompanied by an increase in the production of hydrogen peroxide by mitochondria. It was shown that these actions of derivatives may be due to several effects: the reversion of ATP synthase, changes in the activity of complexes of the respiratory chain and permeabilization of the inner mitochondrial membrane. All compounds also demonstrated the ability to induce aggregation of isolated rat liver mitochondria. Using the model of lecithin liposomes, we found that the F6 conjugate (2 μM) induces the permeability of vesicle membranes for the fluorescent probe sulforhodamine B. High concentrations (25 μM) of the F6 derivative have been found to induce dynamic processes in the liposome membrane leading to aggregation and/or fusion of vesicle membranes. The paper discusses the relationship between the mitochondria-targeted effects of F16-betulinic acid conjugates and their cytotoxicity." @default.
• W3149487008 created "2021-04-13" @default.
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• W3149487008 date "2021-05-01" @default.
• W3149487008 modified "2023-10-03" @default.
• W3149487008 title "Mitochondria-targeted prooxidant effects of betulinic acid conjugated with delocalized lipophilic cation F16" @default.
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• W3149487008 doi "https://doi.org/10.1016/j.freeradbiomed.2021.03.036" @default.
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