Correlação entre potencial eletroquímico e atividade leishmanicida de compostos raros isolados de Fridericia platyphylla (Cham.) L. G. Lohmann

Abstract

Leishmaniasis is a protozoan infection responsible for mortality in several countries. It is a disease neglected because it reaches mainly the low-income population in underdeveloped and developing countries. Currently the treatment is carried out with amphotericin B and pentavalent antimonials, however these have high toxicity, low efficacy and high cost that make treatment difficult. Thus, there is a strong need for safer and more effective treatments against leishmaniasis. In this perspective the present study evaluated the leishmanicidal potential in vitro and in vivo of rare flavonoids isolated from the dichloromeric phase of the roots of Fridericia platyphylla. The isolated substances were named brachydins 1, 2 and 3 and identified by UV, NMR and HPLC-PDA-ESI-IT/MS. The results of the biological tests indicated that brachydins-2 and 3 were active for the amastigote and promastigote forms of the parasite, and brachydin-2 was shown to be more potent for the amastigote form (IC 50 2.20 μM). In addition brachidines 2 and 3 demonstrated low LC50 cytotoxicity of 15.6 and 17.3 μM as compared to the violet control group of gentian LC50 0.48 μM. An electrochemical study of brachydin was carried out in order to correlate the leishmanicidal capacity with the electrochemical potential, considering that the physicochemical properties of drug candidates play an important role in the development and viability of these drugs. The differential pulse and cyclic pulse techniques were used to determine the redox potencies of brachidines-1, 2 and 3, being 0.39 V, 0.60 V and 0.57 V respectively. The pH influence was verified and it was observed that more alkaline pHs facilitate the oxidation of the brachidines and that the electrotransport process of the analyte molecules to the surface of the electrode is controlled by diffusion. It was possible to observe a direct relationship between the oxidation potencies and the leishmanicidal activity of the brachydins, it is believed that the substances that present more positive oxidation potentials favor the leishmanicidal activity, since less positive oxidation potentials lead to the easier oxidation of the compounds, and as a result of this process can cause the biotransformation of the substance, reducing its activity or even.