Avaliação da atividade leishmanicida e antitumoral de novos derivados sintéticos antraquinônicos

Abstract

Quinones are a class among natural compounds, which have multiple therapeutic targets, with different pharmacological affinities. Among its therapeutic actions include: antibacterial, antifungal, antiprotozoal, reaching leishmanicidal and antitumor action. Leishmaniasis are diseases caused by protozoa of the genus Leishmania transmitted through infected sand fly vectors. They are endemic in 98 countries and the population at risk of infection is estimated at 350 million. Among the most fatal tumors, Glioma is the sixth leading cause of death associated with cancer worldwide (75% of malignant brain tumors), its most aggressive form is Glioblastoma with a worldwide incidence of 3.21/100,000 individuals. The treatment adopted in both cases presents a series of adverse events, contraindications and significant toxicity, which can lead the patient to death. Based on the exposed scenario, it is evident the need to seek new therapeutic options for both treatments, with the main focus being therapeutic structures, convenient to act in different pharmacotherapeutic aspects. This study proposes to investigate the leishmanicidal and antitumor activity of new synthetic anthraquinone derivatives (DSAQs). For this, nine DSAQs were developed and provided by the Laboratory of Organic Synthesis – UFMG and by the Laboratory of Electrochemistry LEQUI/UFAL. The in vitro toxicity assay was carried out by the MTT method, on macrophages of the J774.A1 lineage, for the evaluation of the DSAQs. The leishmanicidal activity was evaluated by in vitro parasite viability assay, on extracellular promastigotes forms of Leishmania amazonensis and Leishmania chagasi. The evaluation of antitumor activity was carried out through cell viability assays on Glioblastomas of the GBM02 lineage, using the MTT method. The assay to evaluate the cytotoxic effect on peripheral blood mononuclear cells (PBMC) was carried out. Subsequently, the most promising DSAQs were submitted to tests of: morphological analysis and cell migration. All assays were performed at the Laboratory of Pharmacology and Immunity (LaFI/ICBS/UFAL). In the MTT assay, DSAQs did not reduce 50% of the cell population. Regarding the promastigote assay, ENSJ841, 848, 849 and 854 showed a statistical reduction in parasite viability for L. chagasi species, with ENSJ849 showing a more expressive SI (>35.33) and ENSJ849, 851 and 854 for L. amazonensis species, with ENSJ854 with SI>4.68, better result. In GBM02 cell viability, ENSJ650, 845, 848 and 854 showed tumor reduction after 72 hours treatment. DSAQs were not cytotoxic to PBMC. After these tests, only the DSAQs that showed a reduction in GBM02 cells, proceeded to the morphology tests, and showed signs of cell death with the presence of cells with rounded cytoplasm, cell debris, cytoplasmic vacuoles with extravasation of contents due to the rupture of the cell membrane. These selected DSAQs, in the cell migration assay, were able to statistically significantly inhibit it, where treatment with ENSJ650 migrates only 16% of GBM02. In view of the results, it is possible to state that DSAQs induce a leishmanicidal and antitumor action, corroborating with the multitherapeutic action of quinone derivatives and in the research of new drugs in both areas.