| Author | Fonseca-Berzal, Cristina | |
| Author | Silva, Cristiane França | |
| Author | Menna-Barreto, Rubem F. S. | |
| Author | Batista, Marcos Meuser | |
| Author | Escario, José A. | |
| Author | Arán, Vicente J. | |
| Author | Gómez-Barrio, Alicia | |
| Author | Soeiro, Maria de Nazaré C. | |
| Access date | 2017-02-16T15:10:27Z | |
| Available date | 2017-02-16T15:10:27Z | |
| Document date | 2016 | |
| Citation | FONSECA-BERZAL, Cristina; et al. Biological approaches to characterize the mode of action of two 5-nitroindazolinone prototypes on Trypanosoma cruzi bloodstream trypomastigotes. Parasitology, v.143, n.11, p.1469–1478, Sept. 2016. | pt_BR |
| ISSN | 0031-1820 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/17839 | |
| Language | eng | pt_BR |
| Publisher | Cambridge University Press | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Microscopia eletrônica de transmissão | pt_BR |
| Subject in Portuguese | Doença de Chagas | pt_BR |
| Subject in Portuguese | Autofagia | pt_BR |
| Subject in Portuguese | Citometria de fluxo | pt_BR |
| Subject in Portuguese | Respiração alta resolução | pt_BR |
| Subject in Portuguese | Mitocôndria | pt_BR |
| Title | Biological approaches to characterize the mode of action of two 5-nitroindazolinone prototypes on Trypanosoma cruzi bloodstream trypomastigotes | pt_BR |
| Type | Article | |
| DOI | 10.1017/S0031182016001098 | |
| Abstract | The phenotypic activity of two 5-nitroindazolinones, i.e. 2-benzyl-1-propyl (22) and 2-benzyl-1-butyl (24) derivatives, previously proposed as anti-Trypanosoma cruzi prototypes, was presently assayed on bloodstream trypomastigotes (BT) of the moderately drug-resistant Y strain. Further exploration of putative targets and cellular mechanisms involved in their activity was also carried out. Therefore, transmission electron microscopy, high-resolution respirometry and flow cytometry procedures were performed on BT treated for up to 24 h with the respective EC50 value of each derivative. Results demonstrated that although 22 and 24 were not as active as benznidazole in this in vitro assay on BT, both compounds triggered important damages in T. cruzi that lead to the parasite death. Ultrastructural alterations included shedding events, detachment of plasma membrane and nuclear envelope, loss of mitochondrial integrity, besides the occurrence of a large number of intracellular vesicles and profiles of endoplasmic reticulum surrounding cytoplasmic organelles such as mitochondrion. Moreover, both derivatives affected mitochondrion leading to this organelle dysfunction, as reflected by the inhibition in oxygen consumption and the loss of mitochondrial membrane potential. Altogether, the findings exposed in the present study propose autophagic processes and mitochondrial machinery as part of the mode of action of both 5-nitroindazolinones 22 and 24 on T. cruzi trypomastigotes. | pt_BR |
| Affilliation | CEI Campus Moncloa. UCM-UPM & CSIC. Madrid, Spain / Universidad Complutense de Madrid. Facultad de Farmacia. Departamento de Parasitología. Madrid, Spain. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | CEI Campus Moncloa. UCM-UPM & CSIC. Madrid, Spain / Universidad Complutense de Madrid. Facultad de Farmacia. Departamento de Parasitología. Madrid, Spain. | pt_BR |
| Affilliation | CEI Campus Moncloa. UCM-UPM & CSIC. Madrid, Spain / Consejo Superior de Investigaciones Científicas (CSIC). Instituto de Química Médica (IQM). Madrid, Spain. | pt_BR |
| Affilliation | CEI Campus Moncloa. UCM-UPM & CSIC. Madrid, Spain / Universidad Complutense de Madrid. Facultad de Farmacia. Departamento de Parasitología. Madrid, Spain. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Subject | Chagas disease | pt_BR |
| Subject | autophagy | pt_BR |
| Subject | low cytometry | pt_BR |
| Subject | high-resolution respirometry | pt_BR |
| Subject | mitochondrion | pt_BR |
| Subject | transmission electron microscopy | pt_BR |
| e-ISSN | 1469-8161 | |
| Embargo date | 2030-01-01 | |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
