Author | Meira, Cássio Santana | |
Author | Barbosa Filho, José Maria | |
Author | Rangel, Adriana Lanfredi | |
Author | Guimarães, Elisalva Teixeira | |
Author | Moreira, Diogo Rodrigo Magalhães | |
Author | Soares, Milena Botelho Pereira | |
Access date | 2016-12-12T12:43:14Z | |
Available date | 2016-12-12T12:43:14Z | |
Document date | 2016 | |
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. | pt_BR |
ISSN | 0014-4894 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/16506 | |
Sponsorship | CNPq (grant number 562655/2010-7), PRONEX (grant number 0002/2014), FAPESB (grant number 0042/2013) and FINEP (grant number 01.04.0320-00). | pt_BR |
Language | eng | pt_BR |
Publisher | Elsevier | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Doença de Chagas | pt_BR |
Subject in Portuguese | Trypanosoma cruzi | pt_BR |
Subject in Portuguese | Compostos naturais | pt_BR |
Subject in Portuguese | Semi sintético | pt_BR |
Subject in Portuguese | Triterpenoids | pt_BR |
Subject in Portuguese | Ácido betulínico | pt_BR |
Title | Antiparasitic evaluation of betulinic acid derivatives reveals effective and selective anti-Trypanosoma cruzi inhibitors | pt_BR |
Type | Article | pt_BR |
DOI | 10.1016/j.exppara.2016.04.007 | |
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. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Universidade Federal da Paraíba. Laborat orio de Tecnologia Farmacêutica. João Pessoa, PB, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade do Estado da Bahia. Departamento de Ciências da Vida. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil | pt_BR |
Subject | Chagas disease | pt_BR |
Subject | Trypanosoma cruzi | pt_BR |
Subject | Natural compounds | pt_BR |
Subject | Semi-synthetic | pt_BR |
Subject | Triterpenoids | pt_BR |
Subject | Betulinic acid | pt_BR |