Antileishmanial and antitrypanosomal activity of bufadienolides isolated from the toad Rhinella jimi parotoid macrogland secretion

Antileishmanial and antitrypanosomal activity of bufadienolides isolated from the toad Rhinella jimi parotoid macrogland secretion

Autor Tempone, Andre Gustavo Autor UNIFESP Google Scholar
Pimenta, Daniel Carvalho Google Scholar
Lebrun, Ivo Google Scholar
Sartorelli, Patricia Autor UNIFESP Google Scholar
Taniwaki, Noemi N. Google Scholar
Andrade, Heitor Franco de Google Scholar
Antoniazzi, Marta Maria Google Scholar
Jared, Carlos Google Scholar
Instituição Inst Adolfo Lutz Registro
Universidade Federal de São Paulo (UNIFESP)
Inst Butantan
Universidade de São Paulo (USP)
Resumo Amphibian skin secretions are considered a rich source of biologically active compounds and are known to be rich in peptides, bufadienolides and alkaloids. Bufadienolides are cardioactive steroids from animals and plants that have also been reported to possess antimicrobial activities. Leishmaniasis and American Trypanosomiasis are parasitic diseases found in tropical and subtropical regions. the efforts toward the discovery of new treatments for these diseases have been largely neglected, despite the fact that the only available treatments are highly toxic drugs. in this work, we have isolated, through bioguided assays, the major antileishmanial compounds of the toad Rhinella jimi parotoid macrogland secretion. Mass spectrometry and (1)H and (13)C NMR spectroscopic analyses were able to demonstrate that the active molecules are telocinobufagin and hellebrigenin. Both steroids demonstrated activity against Leishmania (L.) chagasi promastigotes, but only hellebrigenin was active against Trypanosoma cruzi trypomastigotes. These steroids were active against the intracellular amastigotes of Leishmania, with no activation of nitric oxide production by macrophages. Neither cytotoxicity against mouse macrophages nor hemolytic activities were observed. the ultrastructural studies with promastigotes revealed the induction of mitochondrial damage and plasma membrane disturbances by telocinobufagin, resulting in cellular death. This novel biological effect of R. jimi steroids could be used as a template for the design of new therapeutics against Leishmaniasis and American Trypanosomiasis. (C) 2008 Elsevier B.V. All rights reserved.
Assunto Rhinella jimi
Trypanosoma cruzi
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Número do financiamento FAPESP: 05/00974-9
CNPq: 303516/2005-4
CNPq: 473614/20065
Data 2008-07-01
Publicado em Toxicon. Oxford: Pergamon-Elsevier B.V., v. 52, n. 1, p. 13-21, 2008.
ISSN 0041-0101 (Sherpa/Romeo, fator de impacto)
Editor Elsevier B.V.
Extensão 13-21
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000258816500002

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