| Author | Rodrigues, Raquel F. | |
| Author | Pinto, Denise Castro | |
| Author | Echevarria, Aurea | |
| Author | Reis, Camila M. dos | |
| Author | Del Cistia, Catarina N. | |
| Author | Sant´Anna, Carlos Maurício R. | |
| Author | Teixeira, Filipa | |
| Author | Castro, Helena | |
| Author | Cavalheiro, Marilene Canto | |
| Author | Leon, Leonor L. | |
| Author | Tomás, Ana | |
| Access date | 2017-05-23T18:37:19Z | |
| Available date | 2017-05-23T18:37:19Z | |
| Document date | 2012 | |
| Citation | RODRIGUES, Raquel F. et al. Investigation of trypanothione reductase inhibitory activity by 1,3,4-thiadiazolium-2-aminide deritvatives and molecular docking studies. Biorganic & Medicinal Chemistry, v.20, n.1, p.1760-1766, 2012. | pt_BR |
| ISSN | 0968-0896 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/19003 | |
| Language | eng | pt_BR |
| Publisher | Elsevier | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Trypanosoma cruzi | pt_BR |
| Subject in Portuguese | Leishmania sp. | pt_BR |
| Subject in Portuguese | Compostos mesoinicos | pt_BR |
| Title | Investigation of trypanothione reductase inhibitory activity by 1,2,4-thiadiazolium-2-aminide derivatives and molecular docking studies | pt_BR |
| Type | Article | |
| xmlui.metadata.dc.description.abstractes | The biological activities of a series of mesoionic 1,3,4-thiadiazolium-2-aminide derivatives have been studied. The most active compounds (MI-HH; MI-3-OCH3; MI-4-OCH3 and MI-4-NO2) were evaluated to determine their effect on trypanothione reductase (TryR) activity in Leishmania sp. and Trypanosoma cruzi. Among the assayed compounds, only MI-4-NO2 showed enzyme inhibition effect on extracts from different cultures of parasites, which was confirmed using the recombinant enzyme from T. cruzi (TcTryR) and Leishmania infantum (LiTryR). The enzyme kinetics determined with LiTryR demonstrated a non-competitive inhibition profile of MI-4-NO2. A molecular docking study showed that the mesoionic compounds could effectively dock into the substrate binding site together with the substrate molecule. The mesoionic compounds were also effective ligands of the NADPH and FAD binding sites and the NADPH binding site was predicted as the best of all three binding sites. Based on the theoretical results, an explanation at the molecular level is proposed for the MI-4-NO2 enzyme inhibition effect. Given TryR as a molecular target, it is important to continue the study of mesoionic compounds as part of a drug discovery campaign against Leishmaniasis or Chagas’ disease. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal Rural do Rio de Janeiro. Departamento de Química. Seropédica, RJ, Brasil | pt_BR |
| Affilliation | Universidade Federal Rural do Rio de Janeiro. Departamento de Química. Seropédica, RJ, Brasil | pt_BR |
| Affilliation | Universidade Federal Rural do Rio de Janeiro. Departamento de Química. Seropédica, RJ, Brasil | pt_BR |
| Affilliation | Universidade Federal Rural do Rio de Janeiro. Departamento de Química. Seropédica, RJ, Brasil | pt_BR |
| Affilliation | Universidade do Porto. Instituto de Biologia Molecular e Celular. Porto, Portugal. | pt_BR |
| Affilliation | Universidade do Porto. Instituto de Biologia Molecular e Celular. Porto, Portugal. | pt_BR |
| Affilliation | Universidade Federal Rural do Rio de Janeiro. Departamento de Química. Seropédica, RJ, Brasil | pt_BR |
| Affilliation | Universidade Federal Rural do Rio de Janeiro. Departamento de Química. Seropédica, RJ, Brasil | pt_BR |
| Affilliation | Universidade do Porto. Instituto de Biologia Molecular e Celular. Porto, Portugal. | pt_BR |
| Subject | Trypanothione reductase | pt_BR |
| Subject | Mesoionic compounds | pt_BR |
| Subject | Leishmania sp. | pt_BR |
| Subject | Trypanosoma cruzi | pt_BR |
| e-ISSN | 1464-3391 | |
| Embargo date | 2030-01-01 | |
