Repositorio
Institucional

Souza Bombaca, Ana Cristina

Von Dossow, Daniela#Chaves Barbosa, Juliana Magalhaes#Paz, Cristian#Burgos, Viviana#Sadok Menna-Barreto, Rubem Figueiredo

TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in Trypanosoma cruzi

MDPI

MOLECULES

en

Chagas disease is a neglected tropical disease that is caused by the protozoan Trypanosoma cruzi and represents a serious health problem, especially in Latin America. The clinical treatment of Chagas disease is based on two nitroderivatives that present severe side effects and important limitations. In folk medicine, natural products, including sesquiterpenoids, have been employed for the treatment of different parasitic diseases. In this study, the trypanocidal activity of compounds isolated from the Chilean plants Drimys winteri, Podanthus mitiqui and Maytenus boaria on three T. cruzi evolutive forms (epimastigote, trypomastigote and amastigote) was evaluated. Total extracts and seven isolated sesquiterpenoids were assayed on trypomastigotes and epimastigotes. Polygodial (Pgd) from D. winteri, total extract from P. mitiqui (PmTE) and the germacrane erioflorin (Efr) from P. mitiqui were the most bioactive substances. Pgd, Efr and PmTE also presented strong effects on intracellular amastigotes and low host toxicity. Many ultrastructural effects of these substances, including reservosome disruption, cytosolic vacuolization, autophagic phenotype and mitochondrial swelling (in the case of Pgd), were observed. Flow cytometric analysis demonstrated a reduction in mitochondrial membrane potential in treated epimastigotes and an increase in ROS production and high plasma membrane permeability after treatment with Pgd. The promising trypanocidal activity of these natural sesquiterpenoids may be a good starting point for the development of alternative treatmentsforChagas disease.

Artículo original

This research was funded by the Fundacao de Amparo a Pesquisa do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Fundacao Oswaldo Cruz (FIOCRUZ) and Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT-Project: REDI170107).

Esta investigación fue financiada por la Fundacao de Amparo a Pesquisa do Rio de Janeiro (FAPERJ), el Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), la Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), la Fundacao Oswaldo Cruz (FIOCRUZ) y la Comisión Nacional de Investigacion Cientifica y Tecnologica (CONICYT-Proyecto: REDI170107).

10.3390/molecules23112800

pdf

Trypanosoma cruzi# chagas disease# chemotherapy# sesquiterpenoids# mitochondria# autophagy

http://dx.doi.org/10.3390/molecules23112800

Biochemistry & Molecular Biology# Chemistry, Multidisciplinary

Trypanosoma cruzi# enfermedad de Chagas# quimioterapia# sesquiterpenoides# mitocondrias# autofagia

Parasitología

Farmacología y Farmacia

Otras Especialidades de la Biología

WOS:000451641900072

TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in <i>Trypanosoma cruzi</i>

Artículo original

version publicada

MDPI

MOLECULES

Bioquímica y Biología Molecular# Química, Multidisciplinar

en

FAPERJ#CNPq#CAPES#FIOCRUZ#ANID CONICYT REDI170107

FAPERJ

CNPq

CAPES

FIOCRUZ

ANID CONICYT REDI170107

This research was funded by the Fundacao de Amparo a Pesquisa do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Fundacao Oswaldo Cruz (FIOCRUZ) and Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT-Project: REDI170107).

pdf

dorada#verde

acceso abierto

acceso abierto

CC BY

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