RESUMO
Benznidazole is a drug used commonly as a therapeutic agent against Chagas' disease in Brazil. To clarify the cytotoxic action of benznidazole the electrochemical reduction of benznidazole has been investigated using a DNA-electrochemical biosensor, prepared by modification of a glassy carbon electrode with DNA, and the results compared with reduction at a bare glassy carbon electrode. The dependence of peak potential with pH follows slopes of 59 and 52 mV per pH unit in acid media, respectively, which corresponds to a mechanism involving the same number of electrons and protons. In neutral and alkaline solution no significant dependence of peak potential with pH was found. During the electrochemical reduction of benznidazole the formation of the hydroxylamine derivative occurs, involving a total of four electrons. The potentials for reduction were less negative when using the DNA-modified glassy carbon electrode than at the bare glassy carbon electrode although the mechanism was the same, and at pH 7.51 the peak current was four times higher than that obtained with the bare electrode. The DNA-biosensor enabled pre-concentration of the drug onto the electrode surface and the in situ damage caused to the DNA on the electrode surface by the product of benznidazole reduction could be detected electrochemically. The results are in agreement with the hypothesis that the hydroxylamine derivative is the reactive species responsible for the cytotoxic action of benznidazole.
Assuntos
Técnicas Biossensoriais/métodos , Nitroimidazóis/análise , Carbono , Dano ao DNA , DNA de Cadeia Simples , Eletroquímica , EletrodosRESUMO
This paper describes the voltammetric behavior of primaquine as a previous support to the further understanding of the delivery and action mechanisms of its respective synthesized prodrugs. There are few papers describing the drug behavior and most of the time no correlation between oxidation process and pH is done. Our results showed that primaquine oxidation is a one-step reaction involving two electrons with the charge transfer process being strongly pH-dependent in acid medium and pH-independent in a weak basic medium, with the neutral form being easily oxidized. This leads to the conclusion that quinoline nitrogen ring neutralization is a determinant step to the formation of the oxidized primaquine form. The existence of a relationship between the primaquine dissociation equilibrium and its electrooxidation process is shown. This work points the importance of voltammetric methodology as a tool for further studies on quantitative relationship studies between chemical structure and biological activity (QSAR) for electroactive drugs.