Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/15698
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dc.contributor.authorFernandes, M. C.
dc.contributor.authorSilva, E. N. da
dc.contributor.authorPinto, A. V.
dc.contributor.authorCastro, S. L. de
dc.contributor.authorMenna-Barreto, R. F. S.
dc.date.accessioned2016-09-06T14:54:38Z
dc.date.available2016-09-06T14:54:38Z
dc.date.issued2012
dc.identifier.citationFERNANDES, 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.
dc.identifier.issn0031-1820
dc.identifier.urihttps://www.arca.fiocruz.br/handle/icict/15698
dc.language.isoeng
dc.publisherCambridge University Press
dc.rightsrestricted access
dc.subject.otherTrypanosoma cruzi
dc.subject.otherDoença de Chagas
dc.subject.otherQuimioterapia
dc.subject.otherAutofagia
dc.subject.otherNaftoquinonas
dc.subject.otherEspécies de Oxigênio Reativas
dc.subject.otherMitose
dc.titleA novel triazolic naphthofuranquinone induces autophagy in reservosomes and impairment of mitosis in Trypanosoma cruzi
dc.typeArticle
dc.identifier.doi10.1017/S0031182011001612
dc.description.abstractenChagas' 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.
dc.creator.affilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
dc.creator.affilliationUniversidade Federal de Minas Gerais. Instituto de Ciências Exatas. Departamento de Química. Belo Horizonte, MG, Brasil.
dc.creator.affilliationUniversidade Federal do Rio de Janeiro. Núcleo de Pesquisas em Produtos Naturais. Rio de Janeiro, RJ, Brasil.
dc.creator.affilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
dc.creator.affilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
dc.subject.enTrypanosoma cruzi
dc.subject.enChagas Disease
dc.subject.enChemotherapy
dc.subject.enNaphthoquinones
dc.subject.enAutophagy
dc.subject.enMitosis
dc.subject.enReactive oxygen species
dc.identifier.eissn1469-8161
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