Electrochemical activation of β-lapachone in β-cyclodextrin inclusion complexes and reactivity of its reduced form towards oxygen in aqueous solutions

Abstract

Abstract β-Lapachone ( 1 ) is a natural ortho -naphthoquinone that has been shown to have a variety of pharmacological effects, mainly anticancer activity. As a single agent, β-lapachone has demonstrated significant antineoplastic activity against several human cancer cell lines at concentrations typically in the range of 1–10 μM (IC 50 ). The use of cyclodextrins is useful to overcome solubility and bioavailability problems. In the present case, cyclic voltammetry and UV/vis spectroscopy have been used to monitor the inclusion phenomena of β-lapachone within the cavity of β-cyclodextrin, together with studies concerning the competitive effects of ethanol concentration on this behavior. A value of 15 ± 5 M −1 was found for the association constant between β-lapachone and β-cyclodextrin in phosphate buffer, in the presence of 5% ethanol. The electrochemical behavior of the β-lapachone reduced form suggests external interactions between the hydroquinone and β-cyclodextrin via the formation of hydrogen bonds. Electrochemical studies were also performed in the presence of oxygen, since the redox environment of β-lapachone biological targets is considered very important for its therapeutical efficiency. In the presence of O 2 , β-lapachone has shown a catalytic reduction wave, related probably to an electron transfer to oxygen, generating oxygen reactive species and giving back the parent quinone, leading thus to a redox cycle, with a kinetic apparent constant of 40 s −1 . These in vitro results correlate with in vivo activities.