Medicinal Electrochemistry of Halogenated and Nitrated Pterocarpanquinones

Abstract

Electrochemical methods are considered useful tools for simulations of biological redox reactions. The activities of quinones depend on their bioreduction. Biologically active pterocarpanquinones LQB-149 (nitroderivative), 150 and 151 (bromo and chloroderivatives, respectively) were electrochemically investigated by cyclic voltammetry, differential pulse voltammetry, and in situ UV-Vis spectroelectrochemistry, in aprotic media (N,N-dimethylformamide (DMF) + tetra-N-butylammonium (TBAPF 6)). The data obtained regarding their reduction mechanisms, positive reactivity with oxygen and analysis of the electrogenerated intermediates were useful in explaining their biological outcomes. The appearance of bands at 397 and 480 nm, for the halogenated compounds, suggests the generation of transient quinonemethides (QM), electrophilic intermediates related to their activity. As an additional proof for the intermediacy of QM, in the redox processes, chemical reduction of LQB-150, in the presence of hexanethiol was performed and led to a thioalkylated quinone. For the nitroderivative, a broad band appeared at 432 nm, corresponding to the generation of the nitroradical anion, giving rise to a dianion diradical, after reduction at the second wave potential. Computational data correlate well with electrochemical experiments. Homogeneous electron transfer to oxygen, yielding reactive oxygen species, the generation of electrophilic species and the radical reactivity, explain partially the mechanism of biological action.

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.…”

Synthesis and Ameliorative Effect of Isatin–Mesalamine Conjugates on Acetic Acid‐induced Colitis in Rats

“…Thus, the potential mechanism of action of mesalamine involves scavenging these free radical moieties and thereby endorsing the role of antioxidants in the treatment of ulcerative colitis [11]. Isatin, an endogenous moiety with wide spectrum of biological activities, was found to have antioxidant properties along with its protective actions against TNBS-induced colitis in rats [12][13][14][15]. Numerous literature reports are cited on the role of isatin in the modulation of pro-inflammatory mediators such as cytokine production, reduction of leukocyte infiltration, inhibition, expression, and activity of inducible isoforms of cyclooxygenases that are directly involved in the pathogenesis of the colitis [16].…”

“…The synthetic route of all the compounds is summarized in Scheme 1 (3a-d, 4, 5, and 6) and Scheme 2 (9a-g). All the synthesized compounds (3a-d, 4, 5, 6, and 9a-g) were characterized by using the spectral techniques like IR, mass, 1 H NMR, and 13 C NMR, and their physical data are presented in experimental section.…”