Evaluación de la actividad tripanocida de elbasvir y glecaprevir y del efecto sobre la actividad de la enzima Cisteína sintasa de Trypanosoma cruzi in vitro
La enfermedad de Chagas (ECh), causada por el parasito protozoario Trypanosoma cruzi, es una enfermedad endémica y desatendida en las Américas. Debido a su compleja dinámica de transmisión, se ha convertido en un problema de salud pública en el mundo. Actualmente, se cuenta con dos medicamentos para...
- Autores:
-
Chavarrio Cañas, Francy Milena
- Tipo de recurso:
- Fecha de publicación:
- 2023
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/85063
- Palabra clave:
- Parásitos
Parasites
Trypanosoma cruzi
Chagas disease
Cysteine synthase
Trypanocidal activity
Therapeutic target
Enzyme inhibition
Enfermedad de Chagas
Cisteína sintasa
Efecto tripanocida
Blanco terapéutico
Inhibición enzimática
Elbasvir
Glecaprevir
- Rights
- openAccess
- License
- Reconocimiento 4.0 Internacional
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UNACIONAL2_3b02df959f9953fcca49507e6fd2d8da |
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oai:repositorio.unal.edu.co:unal/85063 |
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UNACIONAL2 |
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Universidad Nacional de Colombia |
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|
| dc.title.spa.fl_str_mv |
Evaluación de la actividad tripanocida de elbasvir y glecaprevir y del efecto sobre la actividad de la enzima Cisteína sintasa de Trypanosoma cruzi in vitro |
| dc.title.translated.eng.fl_str_mv |
Evaluation of the trypanocidal activity of elbasvir and glecaprevir and the effect on the activity of the Trypanosoma cruzi cysteine synthase enzyme in vitro |
| title |
Evaluación de la actividad tripanocida de elbasvir y glecaprevir y del efecto sobre la actividad de la enzima Cisteína sintasa de Trypanosoma cruzi in vitro |
| spellingShingle |
Evaluación de la actividad tripanocida de elbasvir y glecaprevir y del efecto sobre la actividad de la enzima Cisteína sintasa de Trypanosoma cruzi in vitro Parásitos Parasites Trypanosoma cruzi Chagas disease Cysteine synthase Trypanocidal activity Therapeutic target Enzyme inhibition Enfermedad de Chagas Cisteína sintasa Efecto tripanocida Blanco terapéutico Inhibición enzimática Elbasvir Glecaprevir |
| title_short |
Evaluación de la actividad tripanocida de elbasvir y glecaprevir y del efecto sobre la actividad de la enzima Cisteína sintasa de Trypanosoma cruzi in vitro |
| title_full |
Evaluación de la actividad tripanocida de elbasvir y glecaprevir y del efecto sobre la actividad de la enzima Cisteína sintasa de Trypanosoma cruzi in vitro |
| title_fullStr |
Evaluación de la actividad tripanocida de elbasvir y glecaprevir y del efecto sobre la actividad de la enzima Cisteína sintasa de Trypanosoma cruzi in vitro |
| title_full_unstemmed |
Evaluación de la actividad tripanocida de elbasvir y glecaprevir y del efecto sobre la actividad de la enzima Cisteína sintasa de Trypanosoma cruzi in vitro |
| title_sort |
Evaluación de la actividad tripanocida de elbasvir y glecaprevir y del efecto sobre la actividad de la enzima Cisteína sintasa de Trypanosoma cruzi in vitro |
| dc.creator.fl_str_mv |
Chavarrio Cañas, Francy Milena |
| dc.contributor.advisor.none.fl_str_mv |
Téllez Meneses, Jair Alexander Romero Calderón, Ibeth Cristina |
| dc.contributor.author.none.fl_str_mv |
Chavarrio Cañas, Francy Milena |
| dc.contributor.researchgroup.spa.fl_str_mv |
Grupo de enfermedades infecciosas - Pontificia Universidad Javeriana Grupo Infecciones y Salud en el Trópico - Universidad Nacional de Colombia sede Bogotá Grupo Zajuna Jwa Samu “Semilla del conocimiento” del Cesar - Universidad Nacional de Colombia sede la Paz |
| dc.subject.decs.spa.fl_str_mv |
Parásitos |
| topic |
Parásitos Parasites Trypanosoma cruzi Chagas disease Cysteine synthase Trypanocidal activity Therapeutic target Enzyme inhibition Enfermedad de Chagas Cisteína sintasa Efecto tripanocida Blanco terapéutico Inhibición enzimática Elbasvir Glecaprevir |
| dc.subject.decs.eng.fl_str_mv |
Parasites |
| dc.subject.proposal.eng.fl_str_mv |
Trypanosoma cruzi Chagas disease Cysteine synthase Trypanocidal activity Therapeutic target Enzyme inhibition |
| dc.subject.proposal.spa.fl_str_mv |
Enfermedad de Chagas Cisteína sintasa Efecto tripanocida Blanco terapéutico Inhibición enzimática |
| dc.subject.proposal.none.fl_str_mv |
Elbasvir Glecaprevir |
| description |
La enfermedad de Chagas (ECh), causada por el parasito protozoario Trypanosoma cruzi, es una enfermedad endémica y desatendida en las Américas. Debido a su compleja dinámica de transmisión, se ha convertido en un problema de salud pública en el mundo. Actualmente, se cuenta con dos medicamentos para su tratamiento, benznidazol (BNZ) y nifurtimox (NFX). Esos medicamentos distan de ser un tratamiento ideal debido a su baja eficacia durante la fase crónica, a los efectos secundarios severos que llevan a una alta tasa de abandono de la terapia, y la menor susceptibilidad que presentan algunas cepas del parásito a estos medicamentos. Esas dificultades en el tratamiento de la ECh, han llevado a la necesidad de buscar nuevas alternativas terapéuticas. En este sentido, la Cisteína sintasa de T. cruzi (TcCS) ha sido estudiada como potencial blanco terapéutico, sobre la cual, se han realizado análisis de biología computacional que han permitido la identificación de moléculas con una alta afinidad y estabilidad de unión al sitio activo de la TcCS, dentro de las cuales se encuentra el elbasvir (EBV) y el glecaprevir (GCV). La presente investigación tuvo como objetivo evaluar in vitro, la actividad tripanocida y el efecto inhibitorio de EBV y de GCV sobre la actividad de la enzima TcCS. El efecto tripanocida de los compuestos fue evaluado en los estadios tripomastigote y amastigote del parásito, la citotoxicidad en células Vero y el efecto sobre la actividad enzimática a partir de extractos de proteínas solubles del parásito. El compuesto EBV presentó actividad biológica contra T. cruzi con una CE50 de 24.22 μM sobre el estadio tripomastigotes y una CI50 de 7.59 μM sobre el amastigote; con un índice de selectividad (IS) estimado de al menos 2.06 en el estadio infectivo y de al menos 6.58 sobre el estadio intracelular. Por su parte, GCV no mostró actividad biológica contra T. cruzi, y su citotoxicidad fue intermedia (CC50: 134.4 μM). Los compuestos evaluados no presentaron una inhibición selectiva de la actividad enzimática de TcCS. En conclusión, EBV presenta una actividad biológica principalmente contra el estadio amastigote de T. cruzi, lo cual hace de éste un posible compuesto líder para el desarrollo de nuevos tratamientos contra la ECh. (Texto tomado de la fuente) |
| publishDate |
2023 |
| dc.date.accessioned.none.fl_str_mv |
2023-12-11T15:24:10Z |
| dc.date.available.none.fl_str_mv |
2023-12-11T15:24:10Z |
| dc.date.issued.none.fl_str_mv |
2023-12 |
| dc.type.spa.fl_str_mv |
Trabajo de grado - Maestría |
| dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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info:eu-repo/semantics/acceptedVersion |
| dc.type.content.spa.fl_str_mv |
Text |
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http://purl.org/redcol/resource_type/TM |
| status_str |
acceptedVersion |
| dc.identifier.uri.none.fl_str_mv |
https://repositorio.unal.edu.co/handle/unal/85063 |
| dc.identifier.instname.spa.fl_str_mv |
Universidad Nacional de Colombia |
| dc.identifier.reponame.spa.fl_str_mv |
Repositorio Institucional Universidad Nacional de Colombia |
| dc.identifier.repourl.spa.fl_str_mv |
https://repositorio.unal.edu.co/ |
| url |
https://repositorio.unal.edu.co/handle/unal/85063 https://repositorio.unal.edu.co/ |
| identifier_str_mv |
Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia |
| dc.language.iso.spa.fl_str_mv |
spa |
| language |
spa |
| dc.relation.references.spa.fl_str_mv |
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Reconocimiento 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Téllez Meneses, Jair Alexanderd50ed986507359558c5372c33a4d1190Romero Calderón, Ibeth Cristina1be6cd68f2562dc4b43f161eb1ab77a0Chavarrio Cañas, Francy Milena2166b81784f5163fde4992da12855beeGrupo de enfermedades infecciosas - Pontificia Universidad JaverianaGrupo Infecciones y Salud en el Trópico - Universidad Nacional de Colombia sede BogotáGrupo Zajuna Jwa Samu “Semilla del conocimiento” del Cesar - Universidad Nacional de Colombia sede la Paz2023-12-11T15:24:10Z2023-12-11T15:24:10Z2023-12https://repositorio.unal.edu.co/handle/unal/85063Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/La enfermedad de Chagas (ECh), causada por el parasito protozoario Trypanosoma cruzi, es una enfermedad endémica y desatendida en las Américas. Debido a su compleja dinámica de transmisión, se ha convertido en un problema de salud pública en el mundo. Actualmente, se cuenta con dos medicamentos para su tratamiento, benznidazol (BNZ) y nifurtimox (NFX). Esos medicamentos distan de ser un tratamiento ideal debido a su baja eficacia durante la fase crónica, a los efectos secundarios severos que llevan a una alta tasa de abandono de la terapia, y la menor susceptibilidad que presentan algunas cepas del parásito a estos medicamentos. Esas dificultades en el tratamiento de la ECh, han llevado a la necesidad de buscar nuevas alternativas terapéuticas. En este sentido, la Cisteína sintasa de T. cruzi (TcCS) ha sido estudiada como potencial blanco terapéutico, sobre la cual, se han realizado análisis de biología computacional que han permitido la identificación de moléculas con una alta afinidad y estabilidad de unión al sitio activo de la TcCS, dentro de las cuales se encuentra el elbasvir (EBV) y el glecaprevir (GCV). La presente investigación tuvo como objetivo evaluar in vitro, la actividad tripanocida y el efecto inhibitorio de EBV y de GCV sobre la actividad de la enzima TcCS. El efecto tripanocida de los compuestos fue evaluado en los estadios tripomastigote y amastigote del parásito, la citotoxicidad en células Vero y el efecto sobre la actividad enzimática a partir de extractos de proteínas solubles del parásito. El compuesto EBV presentó actividad biológica contra T. cruzi con una CE50 de 24.22 μM sobre el estadio tripomastigotes y una CI50 de 7.59 μM sobre el amastigote; con un índice de selectividad (IS) estimado de al menos 2.06 en el estadio infectivo y de al menos 6.58 sobre el estadio intracelular. Por su parte, GCV no mostró actividad biológica contra T. cruzi, y su citotoxicidad fue intermedia (CC50: 134.4 μM). Los compuestos evaluados no presentaron una inhibición selectiva de la actividad enzimática de TcCS. En conclusión, EBV presenta una actividad biológica principalmente contra el estadio amastigote de T. cruzi, lo cual hace de éste un posible compuesto líder para el desarrollo de nuevos tratamientos contra la ECh. (Texto tomado de la fuente)Chagas disease (CD), caused by the protozoan parasite Trypanosoma cruzi, is an endemic and neglected disease in the Americas. Due to its complex transmission dynamics, it has become a public health problem in the world. Currently, there are two medications for its treatment, benznidazole (BNZ) and nifurtimox (NFX). These medications are far from being an ideal treatment due to their low effectiveness during the chronic phase, severe side effects that lead to a high rate of abandonment of therapy, and the lower susceptibility of some strains of the parasite to these medications. These difficulties in the treatment of CD have led to the need to search for new therapeutic alternatives. In this sense, T. cruzi Cysteine synthase (TcCS) has been studied as a potential therapeutic target, on which computational biology analyzes have been conducted that have allowed the identification of molecules with high affinity and stability of binding to the TcCS active site, among which are elbasvir (EBV) and glecaprevir (GCV). The aim of this research was to evaluate in vitro, trypanocidal activity and inhibitory effect of EBV and GCV on the activity of the TcCS enzyme. The trypanocidal effect of the compounds was evaluated in trypomastigote and amastigote stages of the parasite, cytotoxicity in Vero cells and effect on the enzymatic activity from soluble protein extracts of the parasite. The EBV compound presented biological activity against T. cruzi with an EC50 of 24.22 μM on trypomastigote stage and an IC50 of 7.59 μM on amastigote; with an estimated selectivity index (SI) of at least 2.06 in the infective stage and at least 6.58 in the intracellular stage. For its part, GCV did not show biological activity against T. cruzi, and its cytotoxicity was intermediate (CC50: 134.4 μM). The compounds evaluated did not present a selective inhibition of the enzymatic activity of TcCS. In conclusion, EBV presents biological activity mainly against amastigote stage of T. cruzi, which makes it a possible lead compound for the development of new treatments against CD.MaestríaMagíster en Ciencias - MicrobiologíaBiotecnología en saludapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Ciencias - MicrobiologíaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede BogotáEvaluación de la actividad tripanocida de elbasvir y glecaprevir y del efecto sobre la actividad de la enzima Cisteína sintasa de Trypanosoma cruzi in vitroEvaluation of the trypanocidal activity of elbasvir and glecaprevir and the effect on the activity of the Trypanosoma cruzi cysteine synthase enzyme in vitroTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMAguilera, E., Varela, J., Serna, E., Torres, S., Yaluff, G., De Bilbao, N. 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Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases, 12(2), 240–253. https://doi.org/10.1016/j.meegid.2011.12.009ParásitosParasitesTrypanosoma cruziChagas diseaseCysteine synthaseTrypanocidal activityTherapeutic targetEnzyme inhibitionEnfermedad de ChagasCisteína sintasaEfecto tripanocidaBlanco terapéuticoInhibición enzimáticaElbasvirGlecaprevirIdentificación de compuestos inhibidores de la enzima Cisteína Sintasa de Trypanosoma cruzi con potencial actividad tripanocida para el desarrollo de una terapia selectiva contra este parásitoPontificia Universidad JaverianaAdministradoresBibliotecariosConsejerosEstudiantesGrupos comunitariosInvestigadoresMaestrosMedios de comunicaciónPadres y familiasPersonal de apoyo escolarProveedores de ayuda financiera para estudiantesPúblico generalReceptores de fondos federales y solicitantesResponsables políticosLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/85063/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51ORIGINAL1022981858.2023.pdf1022981858.2023.pdfTesis de Maestría en Ciencias - Microbiologíaapplication/pdf1199204https://repositorio.unal.edu.co/bitstream/unal/85063/2/1022981858.2023.pdf9a3f914d01fc94a2fbbff88ed9916820MD52unal/85063oai:repositorio.unal.edu.co:unal/850632023-12-11 10:26:22.434Repositorio Institucional Universidad Nacional de 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