and Leishmanicidal Activity of Beauvericin.

Leishmaniasis is a worldwide disease caused by more than 20 species of parasites. and are among the main causative agents of cutaneous leishmaniasis, presenting a broad spectrum of clinical forms. As these pathologies lead to unsatisfactory treatment outcomes, the discovery of alternative chemotherapeutic options is urgently required. In this investigation, a leishmanicidal bioassay-guided fractionation of the growth media extract produced by P63 led to the isolation of the cyclic depsipeptide beauvericin (). The viability of , and mammalian cells (macrophages and L929 fibroblasts) was assessed in incubated cultures. promastigotes were sensitive to , with EC values ranging from 0.7 to 1.3 μM. Microscopy analysis indicated that spp. parasites showed morphological abnormalities in a dose-dependent manner in the presence of . intracellular amastigotes were more sensitive to than promastigotes (EC = 0.8 ± 0.1 μM), with a good selectivity index (22-30). reduced the infectivity index at very low concentrations, maintaining the integrity of the primary murine host cell for up to the highest concentration tested for . assays of conducted using BALB/c mice infected with stationary-phase promastigotes of in the tail base presented a significant reduction in the lesion parasite load. A second round of assays was performed to assess the efficacy of the topical use of . The results demonstrated a significant decrease in the total ulcerated area of mice treated with when compared with untreated animals. Our results present promising and leishmanicidal effects of beauvericin, emphasizing that systemic inoculation of led to a decrease in the parasite load at the lesion site, whereas topical administration of delayed the progression of leishmaniasis ulcers, a cure criterion established for cutaneous leishmaniasis management.