Lignin from Morinda citrifolia leaves: Physical and chemical characterization, in vitro evaluation of antioxidant, cytotoxic, antiparasitic and ultrastructural activities.

In this work, we investigated in vitro the antioxidant, cytotoxic and anti-leishmanial activities of a lignin extracted from the leaves of Morinda citrifolia. Initially, an analysis of the composition of the sheets was performed, then the lignin was obtained by alkaline delignification and characterized by different techniques: elemental analysis, FT-R, UV-vis, HSQC-NMR, thermal analysis, Py-GC/MS and by GPC. The results showed that the leaves had in their composition cellulose (31.29%), hemicellulose (25.01%), lignin (18.34%), extractives (14.39%) and ash (10.03%). The lignin extraction yield was 89.8%. The lignin obtained is of the GSH type with the following contents 79.39%, 13.58% and 7.03% respectively. Furthermore, it is low molecular weight and thermally stable. It had a phenolic content of 93.3 mg GAE/g and low antioxidant activity. In macrophage cytotoxicity assays, it presented a CC50 of 31.0 µg/mL, showing less toxicity than amphotericin B. In assays against the promastigote forms of Leishmania amazonensis, lignin presented an IC50 of 29.56 µg/mL, a less effective concentration than amphotericin B (IC50 = 0.14 µg/mL). However, it was able to promote inhibition of the parasites, a fact confirmed by structural changes. These findings reinforce that M. citrifolia lignin is a promising macromolecule for use as an antiparasitic and antioxidant agent.

Novel indol-3-yl-thiosemicarbazone derivatives: Obtaining, evaluation of in vitro leishmanicidal activity and ultrastructural studies.

Parasitic diseases still represent serious public health problems, since the high and steady emergence of resistant strains is evident. Because parasitic infections are distributed predominantly in developing countries, less toxic, more efficient, safer and more accessible drugs have become desirable in the treatment of the infected population. This is the case of leishmaniasis, an infectious disease caused by a protozoan of the genus Leishmania sp., responsible for triggering pathological processes from the simplest to the most severe forms leading to high rates of morbidity and mortality throughout the world. In the search for new leishmanicidal drugs, the thiosemicarbazones and the indole fragments have been identified as promising structures for leishmanicidal activity. The present study proposes the synthesis and structural characterization of new indole-thiosemicarbazone derivatives (2a-j), in addition to performing in vitro evaluations through cytotoxicity assays using macrophages (J774) activity against forms of Leishmania infantum and Leishmania amazonensis promastigote as well as ultrastructural analyzes in promastigotes of L. infantum. Results show that the indole-thiosemicarbazone derivatives were obtained with yield values varying from 32.09 to 94.64%. In the evaluation of cytotoxicity, the indole-thiosemicarbazone compounds presented CC50 values between 53.23 and 357.97 µM. Concerning the evaluation against L. amazonensis promastigote forms, IC50 values ranged between 12.31 and  > 481.52 µM, while the activity against L. infantum promastigotes obtained IC50 values between 4.36 and 23.35 µM. The compounds 2d and 2i tested against L. infantum were the most promising in the series, as they showed the lowest IC50 values: 5.60 and 4.36 respectively. The parasites treated with the compounds 2d and 2i showed several structural alterations, such as shrinkage of the cell body, shortening and loss of the flagellum, intense mitochondrial swelling and vacuolization of the cytoplasm leading the parasite to cellular unviability. Therefore, the indole-thiosemicarbazone compounds are promising because they yield considerable synthesis, have low cytotoxicity to mammalian cells and act as leishmanicidal agents.