|Authors:||Vukic, Milena D.|
Vukovic, Nenad L.
|Title:||Redox status, DNA and HSA binding study of naturally occurring naphthoquinone derivatives|
|Abstract:||In the present work we modified the procedure for isolation of naphthoquinones α-methylbutyrylshikon (1), acetylshikonin (2) and β-hydroxyisovalerylshikonin (3) from Onosma visianii Clem. We also investigated possible mechanisms of 1, 2 and 3 as antitumor agents. Accordingly, we estimated concentrations of superoxide anion radical (O2.-), nitrite (NO2 -) and glutathione in HCT-116 and MDA-MB-231 cell lines. Compounds 1 and 3 expressed significant prooxidative activity, while all tested compounds exhibited significant increase in nitrite levels. Also, all examined compounds significantly increased the concentration of oxidized glutathione (GSSG), suggesting significant prooxidative disbalance. The levels of reduced glutathione (GSH) were also elevated as a part of antioxidative cell response. The data indicate that induced oxidative imbalance could be one of the triggers for previously recorded decreased viability of HCT-116 and MDA-MB-231 cells exposed to tested naphthoquinone derivatives. Moreover, we examined interactions mode of compounds 1, 2 and 3 with CT-DNA as one of the crucial targets of many molecules that express cytotoxic activity. The results obtained by UV-visible, fluorescence and molecular docking study revealed that 1, 2 and 3 bound to CT-DNA through minor groove binding. Furthermore, the interactions between HSA and 1, 2 and 3 were examined employing the same methods as for the CT-DNA interaction study. Based on the obtained results, it can be concluded that naphthoquinones 1, 2 and 3 could be effectively transported by human serum albumin. As a conclusion, this study provides further insight of antitumor activity of selected naphthoquinones.|
|Subject Headings:||Naphthoquinone derivatives|
|Appears in Collections:||Original Articles|
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|Vukovic_03012020_proof.pdf||DNB||1.51 MB||Adobe PDF||View/Open|
|Vukovic_03012020_supplementary_data.pdf||DNB||1.87 MB||Adobe PDF||View/Open|
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