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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Tempone, Andre Gustavo [1, 2, 3] ; Pimenta, Daniel Carvalho [4] ; Lebrun, Ivo [4] ; Sartorelli, Patricia [5] ; Taniwaki, Noemi N. [6] ; de Andrade, Jr., Heitor Franco [7] ; Antoniazzi, Marta Maria [1] ; Jared, Carlos [1]
Total Authors: 8
Affiliation:
[1] Inst Butantan, Lab Biol Celular, BR-05503900 Sao Paulo - Brazil
[2] Inst Adolfo Lutz Registro, Dept Parasitol, Lab Toxinol Aplicada, BR-01246000 Sao Paulo - Brazil
[3] Univ Fed Sao Paulo, Dept Morfol & Genet, BR-04023900 Sao Paulo - Brazil
[4] Inst Butantan, Lab Bioquim & Biofis, BR-05503900 Sao Paulo - Brazil
[5] Univ Fed Sao Paulo, Escola Paulista Quim, Dept Ciencias Exatas & Terra, BR-09972270 Diadema, SP - Brazil
[6] Inst Adolfo Lutz Registro, Secao Microscopia Eletron, BR-01246000 Sao Paulo - Brazil
[7] Univ Sao Paulo, Inst Trop Med, Lab Protozool, BR-05304000 Sao Paulo - Brazil
Total Affiliations: 7
Document type: Journal article
Source: Toxicon; v. 52, n. 1, p. 13-21, JUL 2008.
Web of Science Citations: 70
Abstract

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 Ltd. All rights reserved. (AU)

FAPESP's process: 05/00974-9 - Evaluation of the therapeutic potential of amphibian and snake venoms in Leishmaniasis and Chagas' Disease
Grantee:André Gustavo Tempone Cardoso
Support type: Regular Research Grants