| Author | Bourguignon, Saulo C. | |
| Author | Cavalcanti, Danielle F. B. | |
| Author | Souza, Alessandra M. T. de | |
| Author | Castro, Helena C. | |
| Author | Rodrigues, Carlos R. | |
| Author | Albuquerque, Magaly G. | |
| Author | Santos, Dilvani O. | |
| Author | Silva, Gabriel Gomes da | |
| Author | Silva, Fernando C. da | |
| Author | Ferreira, Vitor F. | |
| Author | Pinho, Rosa T. de | |
| Author | Alves, Carlos R. | |
| Access date | 2018-05-17T12:25:33Z | |
| Available date | 2018-05-17T12:25:33Z | |
| Document date | 2011 | |
| Citation | BOURGUIGNON, Saulo C. et al. Trypanosoma cruzi: Insights into naphthoquinone effects on growth and proteinase activity. Experimental Parasitology, v.127, p.160–166, 2011. | pt_BR |
| ISSN | 0014-4894 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/26465 | |
| Language | eng | pt_BR |
| Publisher | Elsevier | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Doença de Chagas | pt_BR |
| Subject in Portuguese | Trypanosoma cruzi | pt_BR |
| Subject in Portuguese | Naftoquinonas | pt_BR |
| Subject in Portuguese | Proteinases | pt_BR |
| Title | Trypanosoma cruzi: insights into naphthoquinone effects on growth and proteinase activity | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.exppara.2010.07.007 | |
| Abstract | In this study we compared the effects of naphthoquinones (α-lapachone, β-lapachone, nor-β-lapachone and Epoxy-α-lap) on growth of Trypanosoma cruzi epimastigotes forms, and on viability of VERO cells. In addition we also experimentally analyzed the most active compounds inhibitory profile against T. cruzi serine- and cysteine-proteinases activity and theoretically evaluated them against cruzain, the major T. cruzi cysteine proteinase by using a molecular docking approach. Our results confirmed β-lapachone and Epoxy-α-lap with a high trypanocidal activity in contrast to α-lapachone and nor-β-lapachone whereas Epoxy-α-lap presented the safest toxicity profile against VERO cells. Interestingly the evaluation of the active compounds effects against T. cruzi cysteine- and serine-proteinases activities revealed different targets for these molecules. β-Lapachone is able to inhibit the cysteine-proteinase activity of T. cruzi proteic whole extract and of cruzain, similar to E-64, a classical cysteine-proteinase inhibitor. Differently, Epoxy-α-lap inhibited the T. cruzi serine-proteinase activity, similar to PMSF, a classical serine-proteinase inhibitor. In agreement to these biological profiles in the enzymatic assays, our theoretical analysis showed that E-64 and β-lapachone interact with the cruzain specific S2 pocket and active site whereas Epoxy-α-lap showed no important interactions. Overall, our results infer that β-lapachone and Epoxy-α-lap compounds may inhibit T. cruzi epimastigotes growth by affecting T. cruzi different proteinases. Thus the present data shows the potential of these compounds as prototype of protease inhibitors on drug design studies for developing new antichagasic compounds. | pt_BR |
| Affilliation | Universidade Federal Fluminense, Instituto de Biologia. Niterói, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal Fluminense, Instituto de Biologia. Niterói, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal Fluminense. Instituto de Química.Departamento de Química Orgânica. Niterói, RJ, Brasil. / Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Laboratório de Modelagem Molecular e QSAR. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal Fluminense, Instituto de Biologia. Niterói, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Laboratório de Modelagem Molecular e QSAR. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Química. Departamento de Química Orgânica. Laboratório de Modelagem Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal Fluminense, Instituto de Biologia. Niterói, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal Fluminense. Instituto de Química.Departamento de Química Orgânica. Niterói, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal Fluminense. Instituto de Química.Departamento de Química Orgânica. Niterói, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Chagas disease | pt_BR |
| Subject | Trypanosoma cruzi | pt_BR |
| Subject | Naphthoquinones | pt_BR |
| Subject | b-Lapachone | pt_BR |
| Subject | Epoxy-a-lap | pt_BR |
| Subject | Proteinases | pt_BR |
| Embargo date | 2010-01-01 | |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
