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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Ihnatenko, Irina | - |
dc.contributor.author | Müller, Marco J. | - |
dc.contributor.author | Orban, Oliver C. F. | - |
dc.contributor.author | Lindhof, Jens C. | - |
dc.contributor.author | Benítez, Diego | - |
dc.contributor.author | Ortíz, Cecilia | - |
dc.contributor.author | Dibello, Estefanía | - |
dc.contributor.author | Seidl, Leonardo L. | - |
dc.contributor.author | Comini, Marcelo A. | - |
dc.contributor.author | Kunick, Conrad | - |
dc.date.accessioned | 2024-03-05T15:53:22Z | - |
dc.date.available | 2024-03-05T15:53:22Z | - |
dc.date.issued | 2023 | - |
dc.identifier.citation | Ihnatenko, I., Müller, M., Orban, O. y otros. "The indole motif is essential for the antitrypanosomal activity of N5-substituted paullones". PloS one [en línea] 2023, v.18, n°11, e0292946, 58 p. DOI: 10.1371/journal. pone.0292946 | es |
dc.identifier.uri | https://hdl.handle.net/20.500.12008/42944 | - |
dc.description.abstract | Severe infections with potentially fatal outcomes are caused by parasites from the genera Trypanosoma and Leishmania (class Kinetoplastea). The diseases affect people of remote areas in the tropics and subtropics with limited access to adequate health care. Besides insufficient diagnostics, treatment options are limited, with tenuous developments in recent years. Therefore, new antitrypanosomal antiinfectives are required to fight these maladies. In the presented approach, new compounds were developed and tested on the target trypa nothione synthetase (TryS). This enzyme is crucial to the kinetoplastids’ unique trypa nothione-based thiol redox metabolism and thus for pathogen survival. Preceding studies have shown that N5 -substituted paullones display antitrypanosomal activity as well as TryS inhibition. Herein, this compound class was further examined regarding the structure-activity relationships (SAR). Diverse benzazepinone derivatives were designed and tested in cell based assays on bloodstream Trypanosoma brucei brucei (T. b. brucei) and intracellular amastigotes of Leishmania infantum (L. infantum) as well as in enzyme-based assays on L. infantum TryS (LiTryS) and T. b. brucei TryS (TbTryS). While an exchange of just the sub stituent in the 9-position of paullones led to potent inhibitors on LiTryS and T. b. brucei para sites, new compounds lacking the indole moiety showed a total loss of activity in both assays. Conclusively, the indole as part of the paullone structure is pivotal for keeping the TryS inhibitory and antitrypanosomal activity of this substance class. | es |
dc.format.extent | 58 p. | es |
dc.format.mimetype | application/pdf | es |
dc.language.iso | en | es |
dc.publisher | PLOS | es |
dc.relation.ispartof | PloS one, v.18, n°11, 2023. -- e0292946 | es |
dc.rights | Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014) | es |
dc.subject.other | PARASITOS | es |
dc.subject.other | INFECCIONES | es |
dc.subject.other | ANTIPARASITARIOS | es |
dc.title | The indole motif is essential for the antitrypanosomal activity of N5-substituted paullones | es |
dc.type | Artículo | es |
dc.contributor.filiacion | Ihnatenko Irina, PVZ–Center of Pharmaceutical Engineering (Alemania). Institute of Medicinal and Pharmaceutical Chemistry | - |
dc.contributor.filiacion | Müller Marco J., PVZ–Center of Pharmaceutical Engineering (Alemania). Institute of Medicinal and Pharmaceutical Chemistry | - |
dc.contributor.filiacion | Orban Oliver C. F., PVZ–Center of Pharmaceutical Engineering (Alemania). Institute of Medicinal and Pharmaceutical Chemistry | - |
dc.contributor.filiacion | Lindhof Jens C., PVZ–Center of Pharmaceutical Engineering (Alemania). Institute of Medicinal and Pharmaceutical Chemistry | - |
dc.contributor.filiacion | Benítez Diego, Instituto Pasteur (Uruguay). Grupo Biología Redox de Tripanosomátidos | - |
dc.contributor.filiacion | Ortíz Cecilia, Instituto Pasteur (Uruguay). Grupo Biología Redox de Tripanosomátidos | - |
dc.contributor.filiacion | Dibello Estefanía, Instituto Pasteur (Uruguay). Grupo Biología Redox de Tripanosomátidos; Universidad de la República (Uruguay) Facultad de Química. Departamento de Química Orgánica. Laboratorio de Síntesis Orgánica. | - |
dc.contributor.filiacion | Seidl Leonardo L., Instituto Pasteur (Uruguay). Grupo Biología Redox de Tripanosomátidos | - |
dc.contributor.filiacion | Comini Marcelo A., Instituto Pasteur (Uruguay). Grupo Biología Redox de Tripanosomátidos | - |
dc.contributor.filiacion | Kunick Conrad, PVZ–Center of Pharmaceutical Engineering (Alemania). Institute of Medicinal and Pharmaceutical Chemistry | - |
dc.rights.licence | Licencia Creative Commons Atribución - No Comercial - Sin Derivadas (CC - By-NC-ND 4.0) | es |
dc.identifier.doi | 10.1371/journal. pone.0292946 | - |
Aparece en las colecciones: | Publicaciones académicas y científicas - Facultad de Química |
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Ihnatenko, I. et al..pdf | Artículo | 5,59 MB | Adobe PDF | Visualizar/Abrir |
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