title: Antileishmanial and antitrypanosomal activity of bufadienolides isolated from the toad Rhinella jimi parotoid macrogland secretion.
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.
authors.affiliation: Laboratório de Toxinologia Aplicada, Departamento de Parasitologia, Instituto Adolfo Lutz, Av. Dr. Arnaldo 355, 8 degrees andar CEP 01246-000, São Paulo, Brazil. atempone@ial.sp.gov.br
authors.forename: André Gustavo
authors.initials: AG
authors.lastname: Tempone
authors.forename: Daniel Carvalho
authors.initials: DC
authors.lastname: Pimenta
authors.forename: Ivo
authors.initials: I
authors.lastname: Lebrun
authors.forename: Patrícia
authors.initials: P
authors.lastname: Sartorelli
authors.forename: Noemi N
authors.initials: NN
authors.lastname: Taniwaki
authors.forename: Heitor Franco
authors.initials: HF
authors.lastname: de Andrade
authors.forename: Marta Maria
authors.initials: MM
authors.lastname: Antoniazzi
authors.forename: Carlos
authors.initials: C
authors.lastname: Jared
mesh_terms: D000818:Animals; D002018:Bufanolides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002025:Bufonidae / Q000378:metabolism*; D006224:Cricetinae; D018314:Leishmania infantum / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D010306:Parotid Gland / Q000378:metabolism*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D002018:Bufanolides; D014344:Trypanocidal Agents; D009569:Nitric Oxide