| Full text | |
| Author(s): Show less - |
de Oliveira Filho, Virlanio A.
;
Gubiani, Juliana R.
;
Borgonovi, Vitoria D.
;
Hilario, Felipe
;
de Amorim, Marcelo R.
;
Minori, Karen
;
Bertolini, Vitor K. S.
;
Ferreira, Antonio G.
;
Biz, Andressa R.
;
Soares, Marcos A.
;
Teles, Helder L.
;
Gadelha, Fernanda R.
;
Berlinck, Roberto G. S.
;
Miguel, Danilo C.
Total Authors: 14
|
| Document type: | Journal article |
| Source: | Journal of Natural Products; v. 87, n. 12, p. 10-pg., 2024-12-03. |
| Abstract | |
Leishmaniasis is a worldwide disease caused by more than 20 species of Leishmania parasites. Leishmania amazonensis and L. braziliensis 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 Aspergillus terreus P63 led to the isolation of the cyclic depsipeptide beauvericin (1). The viability of L. amazonensis, L. braziliensis and mammalian cells (macrophages and L929 fibroblasts) was assessed in 1 incubated cultures. Leishmania promastigotes were sensitive to 1, with EC50 values ranging from 0.7 to 1.3 mu M. Microscopy analysis indicated that Leishmania spp. parasites showed morphological abnormalities in a dose-dependent manner in the presence of 1. L. amazonensis intracellular amastigotes were more sensitive to 1 than promastigotes (EC50 = 0.8 +/- 0.1 mu M), with a good selectivity index (22-30). 1 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 1. In vivo assays of 1 conducted using BALB/c mice infected with stationary-phase promastigotes of L. amazonensis in the tail base presented a significant reduction in the lesion parasite load. A second round of in vivo assays was performed to assess the efficacy of the topical use of 1. The results demonstrated a significant decrease in the total ulcerated area of mice treated with 1 when compared with untreated animals. Our results present promising in vitro and in vivo leishmanicidal effects of beauvericin, emphasizing that systemic inoculation of 1 led to a decrease in the parasite load at the lesion site, whereas topical administration of 1 delayed the progression of leishmaniasis ulcers, a cure criterion established for cutaneous leishmaniasis management. (AU) | |
| FAPESP's process: | 20/01229-5 - Bioactive metabolites of bacterial flora microorganisms from non-filtering marine animals |
| Grantee: | Marcelo Rodrigues de Amorim |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 19/17721-9 - The role of Chemistry in holobiont adaptation |
| Grantee: | Roberto Gomes de Souza Berlinck |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 19/26892-1 - Natural inhibitors of Penicillin-Binding Proteins (PBPs) from marine microorganisms and invertebrates: isolation, identification and mechanism of action |
| Grantee: | Felipe Hilário |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 15/01017-0 - Multi-use instrument approved and awarded in the project 2013/50228-8, name of instrument: ultra-performance liquid chromatograph coupled with a high resolution mass spectrometer |
| Grantee: | Roberto Gomes de Souza Berlinck |
| Support Opportunities: | Multi-user Equipment Program |
| FAPESP's process: | 17/06014-4 - New secondary metabolites of endophytic and marine organisms as proteasome inhibitors: a validated target against cancer |
| Grantee: | Juliana Regina Gubiani |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |