Potencial leishmanicida de produtos microbianos antárticos: avaliação farmacológica de extratos pigmentados bacterianos e revisão sistemática da atividade anti-Leishmania de metabólitos fúngicos

Abstract

Diseases such as leishmaniasis remain neglected by the pharmaceutical industry. As a result, the treatment for this disease is outdated, leaving countless affected individuals unattended. To reverse the impact of this abandonment, it is essential to search for new prototypes of safer drugs for the treatment of leishmaniasis. Therefore, the bioprospecting of natural products, especially microbial products, represents an excellent starting point. From this perspective, this study investigated the leishmanicidal activity of extracts of bacteria isolated from Antarctica, as well as a systematic review of the leishmanicidal activity of fungal metabolites. In the experimental study, eight bacterial isolates obtained from sediment samples and Antarctic lichens were cultivated in nutrient broth for seven days at 15 °C for biomass production. The intracellular pigmented metabolites were extracted with methanol and then the extractive solutions obtained were dried in a desiccator under vacuum. These extracts did not show cytotoxic effect when tested on J774.A1 lineage macrophages in the MTT assay. Furthermore, the extracts demonstrated in vitro leishmanicidal activity against L. (L.) chagasi promastigote forms, highlighting 14.AN.P1 (CI50 = 63.04 ± 5.49 µg/mL), 2.ANUV.P4 (CI50 = 91.19 ± 3.69 µg/mL), 14.UVAB.11 (CI50 = 52.65 ± 2.91 µg/mL), 4.UVAB.12 (CI50 = 36.83 ± 2.61 µg/mL), and 7.UVAB.14 (CI50 = 78.10 ± 4.42 µg/mL). However, no extarct inhibited the growth of L. (L.) amazonensis promastigote forms. In the systematic review, conducted from searches in the PubMed, Lilacs and Scielo databases, 59 articles were included, of which 39 (66.1%) presented at least one isolated compound with leishmanicidal activity, while 20 (33.9%) evaluated Only crude extracts or semi-purified fractions. The active compounds reported were mainly produced by Penicillium sp. and Aspergillus sp. The species of L. (L.) amazonensis and L. (L.) donovani were the most evaluated. The results obtained in the experimental study, together with the evidence reported by the publications gathered in the systematic review, indicate a promising path towards the development of new chemical entities to combat leishmaniasis in the prospecting of microbial products.