Structural design, synthesis and anti-Trypanosoma cruzi profile of the second generation of 4-thiazolidinones chlorine derivatives.

Chagas disease causes more deaths in the Americas than any other parasitic disease. Initially confined to the American continent, it is increasingly becoming a global health problem. In fact, it is considered to be an "exotic" disease in Europe, being virtually undiagnosed. Benznidazole, the only drug approved for treatment, effectively treats acute-stage Chagas disease, but its effectiveness for treating indeterminate and chronic stages remains uncertain. Previously, our research group demonstrated that 4-thiazolidinones presented anti-T. cruzi activity including in the in vivo assays in mice, making this fragment appealing for drug development. The present work reports the synthesis and anti-T. cruzi activities of a novel series of 4-thiazolidinones derivatives that resulted in an increased anti-T. cruzi activity in comparison to thiosemicarbazones intermediates. Compounds 2c, 2e, and 3a showed potent inhibition of the trypomastigote form of the parasite at low cytotoxicity concentrations in mouse splenocytes. Besides, all the 2c, 2e, and 3a tested concentrations showed no cytotoxic activity on macrophages cell viability. When macrophages were submitted to T. cruzi infection and treated with 2c and 3a, compounds reduced the release of trypomastigote forms. Results also showed that the increased trypanocidal activity induced by 2c and 3a is independent of nitric oxide release. Flow cytometry assay showed that compound 2e was able to induce necrosis and apoptosis in trypomastigotes. Parasites treated with the compounds 2e, 3a, and 3c presented flagellum shortening, retraction and curvature of the parasite body, and extravasation of the internal content. Together, these data revealed a novel series of 4-thiazolidinones fragment-based compounds with potential effects against T. cruzi and lead-like characteristics.

Gamma irradiation for enhancing active chemical compounds in leaf extracts of Libidibia ferrea (Leguminosae).

This research was designed to evaluate the influence of the irradiation process of the leaf extracts of Libidibia ferrea (Leguminosae) on the production of secondary chemical compounds, including their biological activity. Leaves were collected and prepared to obtain the crude extract, which was then aliquoted and separately exposed to a Co-60 source with different doses, namely: 5, 7, 10, 12, 15, 20, 25, and 30 kGy. From irradiated and control samples, tests of toxicity were carried out with the microcrustacea Artemia salina Leach at three moments: 24 h, 60 and 180 days after the irradiation of the samples. Bioassays showed an increase in the toxicity of the irradiated extracts, correlated with the dose. The toxicity level did not change with the storage time, indicating the excellent stability of the samples. To assess the phytochemical profile of the crude and irradiated extracts, three techniques were employed: thin-layer chromatography (TLC), liquid chromatography coupled to mass spectrometry (LC-MS), and gas chromatography coupled to mass spectrometry (GC-MS). The phytochemical results emphasized the presence of phenols, tannins, and triterpenes. The analytical tests confirmed the role of ionizing radiation in breaking down macromolecules into simpler chemical species responsible for increasing chemical activity of the extract. This report presents and discusses ionizing radiation as an outstanding tool for enhancing active chemical compounds in leaf extracts of Libidibia ferrea, which reflects on their biochemical properties.