Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/15698
Title: A novel triazolic naphthofuranquinone induces autophagy in reservosomes and impairment of mitosis in Trypanosoma cruzi
Authors: Fernandes, M. C.
Silva, E. N. da
Pinto, A. V.
Castro, S. L. de
Menna-Barreto, R. F. S.
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Exatas. Departamento de Química. Belo Horizonte, MG, Brasil.
Universidade Federal do Rio de Janeiro. Núcleo de Pesquisas em Produtos Naturais. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Abstract: Chagas' disease, caused by the protozoan Trypanosoma cruzi, represents a serious health problem in Latin America, and the available chemotherapy, which is based on 2 nitro-derivatives, is not satisfactory. In folk medicine, natural products including naphthoquinones have been employed for the treatment of different parasitic diseases. In the pursuit of alternative drugs for Chagas' disease, we investigated the mechanism of action of the triazolic naphthoquinone (TN; 2,2-dimethyl-3-(4-phenyl-1H-1,2,3-triazol-1-yl)-2,3-dihydronaphtho[1,2-b]furan-4,5-dione), which is the most active compound against T. cruzi trypomastigotes among a series of naphthofuranquinones. TN was active against the 3 parasite forms producing a dose-dependent inhibitory effect. In epimastigotes, TN induced reservosome disruption, flagellar blebbing, Golgi disorganization, the presence of cytosolic concentric membrane structures and abnormal multiflagellar parasites. The treatment also led to the appearance of well-developed endoplasmic reticulum profiles surrounding organelles that associated with an increase in monodansylcadaverine labelling, suggesting autophagy as part of the TN mechanism of action. Interestingly, no ultrastructural damage was detected in the mitochondria of naphthoquinone-treated epimastigotes. Flow cytometric analysis demonstrated an impairment of mitosis, an increase in ROS production and the maintenance of mitochondrial membrane potential. TN could be a good starting point in the investigation of a chemotherapeutic approach for the treatment of Chagas' disease.
Keywords: Trypanosoma cruzi
Chagas Disease
Chemotherapy
Naphthoquinones
Autophagy
Mitosis
Reactive oxygen species
keywords: Trypanosoma cruzi
Doença de Chagas
Quimioterapia
Autofagia
Naftoquinonas
Espécies de Oxigênio Reativas
Mitose
Issue Date: 2012
Publisher: Cambridge University Press
Citation: FERNANDES, M. C. et al. A novel triazolic naphthofuranquinone induces autophagy in reservosomes and impairment of mitosis in Trypanosoma cruzi. Parasitology, v.139, n.1, p.26-36, Jan. 2012.
DOI: 10.1017/S0031182011001612
ISSN: 0031-1820
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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