Electrochemical characterization of shikonin and in-situ evaluation of interaction with DNA

Abstract

• Shikonin, a natural compound with pharmaceutical properties; • Shikonin reduction results in semiquinone radical and superoxide; • Shikonin induces DNA conformational modification. • In-situ shikonin reduction leads to occurrence 8-oxo-guanine. • Shikonin-DNA interaction mechanism proposed. Shikonin, a natural compound with pharmaceutical properties, has attracted interest due to its anti-oxidant properties, potential anti-cancer activity and activity over several biological pathways, such as dsDNA transcription/replication of cancer cells and inhibition of pyruvate kinase M2. The electrochemical behavior of shikonin in aqueous media was investigated at glassy carbon electrodes by cyclic and differential pulse voltammetry. The reduction involves the quinone moiety and formation of a semiquinone intermediate. In the absence of dissolved oxygen, the reduction is reversible while in normal atmosphere leads to formation of superoxide cation. The oxidation occurs at the dihydroxy moiety and reversibility was only observed in acid electrolytes. A redox mechanism was proposed. The interaction between shikonin and ds DNA was evaluated in incubated solutions and in situ with the dsDNA-electrochemical biosensor. The mechanism of interaction is time-dependent and follows an initial binding step at the grooves of the double strand leading to conformational modifications recognized through the variation of guanine and adenine oxidation peaks. The in-situ electrochemical production of the semiquinone intermediate leads to a preferential interaction with guanine residues, promoting their oxidation and consequently occurrence 8-oxo-guanine. An interaction mechanism was proposed.