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 (TBAPF6)). 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.

As pterocarpanquinonas 8a-c, previamente sintetizadas em nosso laboratório, e uma série homóloga de derivados, substâncias 9a-c preparadas neste trabalho, foram avaliadas em células de câncer de mama (MCF-7) e em cultura dos parasitas Leishmania amazonensis e Plasmodium falciparum. As substâncias 8a-c foram mais potentes que 9a-c nas células tumorais e em Leishmania amazonensis. Por outro lado, 9a-c mostraram ser as mais ativas sobre o Plasmodium falciparum. Todas as substâncias estudadas foram biosseletivas, apresentando baixa citotoxicidade para linfócitos murinos frescos e linfócitos humanos ativados pelo mitógeno fitoemoaglutinina (PHA).

Pterocarpanquinones 8a-c, previously synthesized in our laboratory, and an homologous series of derivatives, compounds 9a-c prepared in this work, were evaluated on breast cancer cells (MCF-7) and on the parasites Leishmania amazonensis and Plasmodium falciparum, in culture. Compounds 8a-c were more potent than 9a-c on tumor cells and Leishmania amazonensis. On the other hand, 9a-c showed to be more active on Plasmodium falciparum. All the compounds studied were bioselective, presenting negligible cytotoxicity against fresh murine lymphocytes and human lymphocytes activated by the mitogen phytohemaglutinin (PHA).

Apresentamos a primeira síntese do (±)-3,4-diidroxi-8,9-metilenodioxipterocarpano, um isoflavonóide natural que apresenta atividade antitumoral. A etapa chave envolveu uma arilação de Heck entre o 7,8-dibenziloxicromeno e o organomercurial derivado do sesamol, seguido de reação de desbenzilação. O aduto de Heck foi também empregado na síntese do correspondente derivado cumestano, utilizando DDQ como agente oxidante.

We report the first synthesis of (±)-3,4-dihydroxy-8,9-methylenedioxypterocarpan, a natural isoflavonoid that shows antitumoral activity. The key step involved the Heck reaction between the 7,8-dibenzyloxychromen and the organomercurial derived from sesamol, followed by debenzylation. The Heck adduct was also employed in the synthesis of the corresponding coumestan derivative, using DDQ as oxidant agent.