Reactive Oxygen Species Release, Alkylating Ability, and DNA Interactions of a Pterocarpanquinone: A Test Case for Electrochemistry

Abstract

The electrochemistry of a redox‐based bioactive pterocarpanquinone, designated as LQB‐118, and its precursor chromenquinone (CQ) was investigated in protic and aprotic media with a focus on the reduction mechanism in both media, the reactivity with oxygen, and the interaction with biological targets, such as DNA. UV/Vis spectroelectrochemistry clarified the proposed mechanism. The appearance of bands at λ=331, 400, and 600 nm suggests the generation of transient quinonemethides (QM). Electrochemical experiments revealed homogeneous electron transfer to oxygen. LQB‐118 itself interacts with calf‐thymus DNA and ssDNA in solution. It, and its electrogenerated intermediates, have been shown to decrease the diagnostic oxidation peaks of guanosine and adenosine residues. These results, together with electrochemical evidence for the formation of QMs and the reductive addition of thiols, partly explain the reported cytotoxic and parasiticidal effects of this quinone. Overall, the electrochemical methods do well to predict the molecular mechanism of the biological activity of the present class of compounds. As an additional competitive advantage, electrochemistry allows reductive cleavage in situ, the characterization of the generated intermediate, the calculation of the number of transferred electrons, and positively mimics in vitro and in vivo experiments.

Carajurin Induces Apoptosis in Leishmania amazonensis Promastigotes through Reactive Oxygen Species Production and Mitochondrial Dysfunction

“…Both oxidation processes showed some reversibility; however, the cathodic peaks showed slower processes, resulting in lower peak currents [ 17 ]. As shown in Figure 7 (green line), when scanning at more negative potentials, the carajurin in oxygen absence showed a reversible process in potential,1.07 V vs. Ag/Ag + (–1.12 V vs. NHE), which indicated the compound’s ability to capture electrons forming a radical anion, a factor that influences in the compound’s properties [ 18 , 19 ]. Figure 7 (red line) shows the voltammetric response in an air-saturated electrolyte solution, associated with superoxide radical generation, in the absence of carajurin.…”

“…Cyclic voltammetry (CV) is a simple method for screening active redox compounds and estimating electrochemical activity in different samples, such as medicinal plants [ 17 ]. To analyze the mode of action of carajurin, the electrochemical behavior of the compound was analyzed by CV in an aprotic organic environment (dichloromethane), in order to mimic the nonpolar cellular environment [ 18 , 19 ]. Under aerobic conditions, the compound reduction mechanism predominates, resulting in the radical anion intermediate, which, when undergoing a retro-oxidation process in the presence of oxygen, releases ROS, similar to the process described for other compounds in actions against parasites [ 18 , 19 , 44 , 45 ].…”

“…To analyze the mode of action of carajurin, the electrochemical behavior of the compound was analyzed by CV in an aprotic organic environment (dichloromethane), in order to mimic the nonpolar cellular environment [ 18 , 19 ]. Under aerobic conditions, the compound reduction mechanism predominates, resulting in the radical anion intermediate, which, when undergoing a retro-oxidation process in the presence of oxygen, releases ROS, similar to the process described for other compounds in actions against parasites [ 18 , 19 , 44 , 45 ]. When analyzing the electroactivity of carajurin, it can be observed that in the absence of molecular oxygen ( Figure 7 , green line) the compound shows a reduction process, which can lead to the generation of the radical intermediate.…”

“…When analyzing the electroactivity of carajurin, it can be observed that in the absence of molecular oxygen ( Figure 7 , green line) the compound shows a reduction process, which can lead to the generation of the radical intermediate. As seen in Figure 7 (blue line), in the presence of molecular oxygen, the voltammogram shows a change in the profile, indicating a possible interaction of carajurin electroreduction products with dissolved oxygen in the electrochemical cell [ 18 , 19 ]. These effects include a shift from the position of the peak of carajurin reduction, for more positive potentials.…”