Produção e avaliação da atividade leishmanicida de extratos de fungos isolados da Antártica e prospecção tecnológica de metabólitos fúngicos

Abstract

Leishmaniasis is a neglected, infectious, and non-contagious disease caused by parasites of the genus Leishmania. Leishmania has two evolutionary forms, promastigote and amastigote, and two main clinical manifestations: cutaneous and visceral, with the latter being of greater concern as it can lead to the patient's death if untreated. Despite the complexity of the disease, the therapeutic arsenal remains limited, with pentavalent antimonials being the first choice and drugs like amphotericin B and pentamidine as the second choice. However, this therapy presents undesirable adverse effects, along with significant cytotoxicity and parasitic resistance. In light of this issue, the present study evaluated extracts from fungus producing secondary metabolites from Antarctica, and also conducted a patent review regarding the leishmanicidal activity of fungal metabolites. In the experimental study, the biomass of these fungi was produced, followed by solvent extraction using ethyl acetate and acetone, pigment concentration, drying, dilution, cell viability tests (MTT), and evaluation of leishmanicidal activity against the promastigote form of L. amazonensis and L. chagasi. Yeast extracts (19L15, 4L2, 2L19, NL1, and GL19) and filamentous fungus extracts (4FFLQ2, 5YP4, 2FFLQ6 acetate, 2FFLQ6 acetone, 1EMP1, 3EMP4, and 2EMP4) were produced and tested at concentrations of 100, 30, 10, 3, 1, and 0.3 µg/mL. In the cell viability assay, the maximum cytotoxic effect found for yeast extracts was 40.54 ± 3.37%; 24.37 ± 3.66%; 29.09 ± 3.57%; 6.28 ± 1.00%; 22.98 ± 1.63%, respectively. The cytotoxic effect of filamentous fungi was: 60.53 ± 2.50%; 67.33 ± 1.51%; 19.68 ± 6.62%; 19.68 ± NA; 23.38 ± 7.16%; 17.30 ± 10.59%; NA and NA. In the assay to evaluate leishmanicidal activity, the tested yeast extracts (for both species) and filamentous fungus extracts (for L. chagasi) were not lethal to the parasites even at the maximum tested concentration of 100 µg/mL. The extracts 2FFLQ6 acetate and 2FFLQ6 acetone exhibited a maximum effect of 74.36 ± 4.10% and 84.62 ± 5.32% against the L. amazonensis species, suggesting the need for further studies in this area. In the patent review, patents from 2012-2022 that were within the thematic area were selected, which demonstrated activity against L. major, L. amazonensis, and L. donovani species, along with low toxicity. Despite the results, the subject is still underexplored by the scientific community, and the continuation and encouragement of bioprospecting research using fungal isolates and extracts is warranted.