Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/16506
Title: Antiparasitic evaluation of betulinic acid derivatives reveals effective and selective anti-Trypanosoma cruzi inhibitors
Authors: Meira, Cássio Santana
Barbosa Filho, José Maria
Rangel, Adriana Lanfredi
Guimarães, Elisalva Teixeira
Moreira, Diogo Rodrigo Magalhães
Soares, Milena Botelho Pereira
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Universidade Federal da Paraíba. Laborat orio de Tecnologia Farmacêutica. João Pessoa, PB, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade do Estado da Bahia. Departamento de Ciências da Vida. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Abstract: Betulinic acid is a pentacyclic triterpenoid with several biological properties already described, including antiparasitic activity. Here, the anti-Trypanosoma cruzi activity of betulinic acid and its semi-synthetic amide derivatives (BA1-BA8) was investigated. The anti-Trypanosoma cruzi activity and selectivity were enhanced in semi-synthetic derivatives, specially on derivatives BA5, BA6 and BA8. To understand the mechanism of action underlying betulinic acid anti-T. cruzi activity, we investigated ultrastructural changes by electron microscopy. Ultrastructural studies showed that trypomastigotes incubated with BA5 had membrane blebling, flagella retraction, atypical cytoplasmic vacuoles and Golgi cisternae dilatation. Flow cytometry analysis showed that parasite death is mainly caused by necrosis. Treatment with derivatives BA5, BA6 or BA8 reduced the invasion process, as well as intracellular parasite development in host cells, with a potency and selectivity similar to that observed in benznidazole-treated cells. More importantly, the combination of BA5 and benznidazole revealed synergistic effects on trypomastigote and amastigote forms of T. cruzi. In conclusion, we demonstrated that BA5 compound is an effective and selective anti-T. cruzi agent.
Keywords: Chagas disease
Trypanosoma cruzi
Natural compounds
Semi-synthetic
Triterpenoids
Betulinic acid
keywords: Doença de Chagas
Trypanosoma cruzi
Compostos naturais
Semi sintético
Triterpenoids
Ácido betulínico
Issue Date: 2016
Publisher: Elsevier
Citation: MEIRA, C. S. et al. Antiparasitic evaluation of betulinic acid derivatives reveals effective and selective anti-Trypanosoma cruzi inhibitors. Experimental Parasitology, v. 166, p. 108e115, 2016.
DOI: 10.1016/j.exppara.2016.04.007
ISSN: 0014-4894
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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