Isolation, characterization, antileishmanial and antitrypanosomal activity of bioactive compounds from brazilian amphibian poisons

Author(s)

Erika Gracielle Pinto

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Medicina Tropical de São Paulo (IMT)
• Defense date: 2012-02-29

Examining board members

André Gustavo Tempone Cardoso; Patrick Jack Spencer

• Advisor: André Gustavo Tempone Cardoso

Abstract

Among the tropical parasitic diseases, those caused by protozoa present a major challenge to public health, being represented by leishmaniasis and Chagas disease. Affect large populations marginal to the global economic process, and thus are not seen as potential markets. This project aimed the isolation of new natural compounds in animal venoms with anti-Leishmania activity and anti-T. cruzi. The present study fractionated by different chromatographic techniques, the poisons of the amphibians Siphonops annulatus, Corythomantis greeningi, Aparasphenodon brunoi and Phyllomedusa hypochondrialis, aiming the isolation of peptides and secondary metabolites through bioguided assays. By using mass spectrometry and sequencing by Edman degradation, it was possible to do the biochemical characterization of five active peptides from the poison of Phyllomedusa hypochondrialis, as bradykinin, dermaseptins 1 and 4 and phylloseptins 7 and 8. The peptides showed a 50% Effective Concentration (EC50) ranging from 0.7 to 20 ?g/mL in L. (L.) infantum chagasi and T. cruzi, with little or no cytotoxicity to mammalian cells at the tested concentrations. In addition, the chemical separation of the poison of the amphibian Siphonops annulatus provided a highly active fraction against promastigotes of L. (L.) infantum chagasi, with an EC50 of 0.065 ?g/mL, but highly toxicity to peritoneal macrophages and without selectivity against the intracellular forms of Leishmania. Ultrastructural studies of Leishmania showed severe mitochondrial damages and the formation of large cytoplasmic vacuoles, leading to parasite death within few hours. The present study demonstrated the potential of peptides and secondary metabolites of amphibian poisons, and if adequately studied, may contribute as prototypes of new drugs for neglected diseases. (AU)

• FAPESP's process: 09/12236-3 - Isolation, characterization, antileishmanial and antitrypanosomal activity of bioactive compounds from Brazilian amphibian poisons
• Grantee: Érika Gracielle Pinto
• Support Opportunities: Scholarships in Brazil - Master