Arylated α- and β-dihydrofuran naphthoquinones: Electrochemical parameters, evaluation of antitumor activity and their correlation

We herein report the antitumor activity of several substituted α- and β-dihydrofuran naphthoquinones against 4 human tumor cell lines, HL-60 (leukemia), SF-295 (CNS), HCT-8 (colon) and MDA-MB435 (melanoma), and their electrochemical parameters, in the absence and presence of oxygen, in comparison with their non-substituted precursors. These compounds were prepared from readily available lawsone and olefins in the presence of cerium (IV) ammonium nitrate. The β-dihydrofuran naphthoquinones were shown to be highly cytotoxic, while their positional α-isomers were considered less active. The level of intracellular ROS release and the first wave redox potentials were also analyzed and compared with the kinetic constants of the reactivity of quinones with oxygen (kapp) obtained through cyclic voltammetry. Significantly positive correlations between ROS release and oxygen reactivity were obtained, while IC50vs. ROS release; −EpIcvs. kapp or ROS values correlated in an inverse manner, i.e., the less negative the potential, higher the activities. These findings reinforce the effectiveness of the combination of pharmacology and electrochemistry in medicinal chemistry, in the search of lead anticancer compounds.