Redox status, DNA and HSA binding study of naturally occurring naphthoquinone derivatives

Milena D Vukic; Nenad L Vukovic; Ana Obradovic; Milos Matic; Maja Djukic; Edina Avdovic

doi:10.17179/excli2019-1859

Redox status, DNA and HSA binding study of naturally occurring naphthoquinone derivatives

EXCLI J. 2020 Jan 3:19:48-70. doi: 10.17179/excli2019-1859. eCollection 2020.

Authors

Milena D Vukic¹, Nenad L Vukovic¹, Ana Obradovic², Milos Matic², Maja Djukic¹, Edina Avdovic^{1

3}

Affiliations

¹ Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovica 12, 34000 Kragujevac, Serbia.
² Department of Biology and Ecology, Faculty of Science, University of Kragujevac, Radoja Domanovica 12, 34000 Kragujevac, Serbia.
³ Department of Sciences, Institute for Information Technologies Kragujevac, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, Serbia.

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.

Keywords: DNA interactions; HSA interactions; breast cancer; colon cancer; naphthoquinone derivatives; redox status.