Síntesis de híbridos cumarina-chalcona y evaluación de la actividad antiparasitaria in vitro

Ilustraciones, fotos

Autores:
Valencia Cossio, Sebastián
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/85629
Acceso en línea:
https://repositorio.unal.edu.co/handle/unal/85629
https://repositorio.unal.edu.co/
Palabra clave:
540 - Química y ciencias afines
Medicina tropical
Enfermedades parasitarias
Infecciones por protozoarios
Cumarinas
Agentes antiparasitarios
Trypanosoma cruzii
Leishmaniasis
T. cruzi
L. braziliensis
Actividad biológica
Híbridos
Cumarinas
Chalconas
Leishmaniasis cutánea
Chalcona
Rights
openAccess
License
Atribución-NoComercial-SinDerivadas 4.0 Internacional
id UNACIONAL2_85d5a6e899c77ae4c43a9e4ae307b16c
oai_identifier_str oai:repositorio.unal.edu.co:unal/85629
network_acronym_str UNACIONAL2
network_name_str Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv Síntesis de híbridos cumarina-chalcona y evaluación de la actividad antiparasitaria in vitro
dc.title.translated.eng.fl_str_mv Synthesis of coumarin-chalcone hybrids and evaluation of antiparasitic activity in vitro
title Síntesis de híbridos cumarina-chalcona y evaluación de la actividad antiparasitaria in vitro
spellingShingle Síntesis de híbridos cumarina-chalcona y evaluación de la actividad antiparasitaria in vitro
540 - Química y ciencias afines
Medicina tropical
Enfermedades parasitarias
Infecciones por protozoarios
Cumarinas
Agentes antiparasitarios
Trypanosoma cruzii
Leishmaniasis
T. cruzi
L. braziliensis
Actividad biológica
Híbridos
Cumarinas
Chalconas
Leishmaniasis cutánea
Chalcona
title_short Síntesis de híbridos cumarina-chalcona y evaluación de la actividad antiparasitaria in vitro
title_full Síntesis de híbridos cumarina-chalcona y evaluación de la actividad antiparasitaria in vitro
title_fullStr Síntesis de híbridos cumarina-chalcona y evaluación de la actividad antiparasitaria in vitro
title_full_unstemmed Síntesis de híbridos cumarina-chalcona y evaluación de la actividad antiparasitaria in vitro
title_sort Síntesis de híbridos cumarina-chalcona y evaluación de la actividad antiparasitaria in vitro
dc.creator.fl_str_mv Valencia Cossio, Sebastián
dc.contributor.advisor.none.fl_str_mv Durango Restrepo, Diego Luis
Gil González, Jesús Humberto
dc.contributor.author.none.fl_str_mv Valencia Cossio, Sebastián
dc.subject.ddc.spa.fl_str_mv 540 - Química y ciencias afines
topic 540 - Química y ciencias afines
Medicina tropical
Enfermedades parasitarias
Infecciones por protozoarios
Cumarinas
Agentes antiparasitarios
Trypanosoma cruzii
Leishmaniasis
T. cruzi
L. braziliensis
Actividad biológica
Híbridos
Cumarinas
Chalconas
Leishmaniasis cutánea
Chalcona
dc.subject.lemb.none.fl_str_mv Medicina tropical
Enfermedades parasitarias
Infecciones por protozoarios
Cumarinas
Agentes antiparasitarios
Trypanosoma cruzii
Leishmaniasis
dc.subject.proposal.spa.fl_str_mv T. cruzi
L. braziliensis
Actividad biológica
Híbridos
Cumarinas
Chalconas
dc.subject.wikidata.none.fl_str_mv Leishmaniasis cutánea
Chalcona
description Ilustraciones, fotos
publishDate 2023
dc.date.issued.none.fl_str_mv 2023-01-22
dc.date.accessioned.none.fl_str_mv 2024-02-05T21:50:21Z
dc.date.available.none.fl_str_mv 2024-02-05T21:50:21Z
dc.type.spa.fl_str_mv Trabajo de grado - Maestría
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/masterThesis
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/acceptedVersion
dc.type.content.spa.fl_str_mv Text
dc.type.redcol.spa.fl_str_mv http://purl.org/redcol/resource_type/TM
status_str acceptedVersion
dc.identifier.uri.none.fl_str_mv https://repositorio.unal.edu.co/handle/unal/85629
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/85629
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.indexed.spa.fl_str_mv LaReferencia
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dc.publisher.program.spa.fl_str_mv Medellín - Ciencias - Maestría en Ciencias - Química
dc.publisher.faculty.spa.fl_str_mv Facultad de Ciencias Exactas y Naturales
dc.publisher.place.spa.fl_str_mv Medellín, Colombia
dc.publisher.branch.spa.fl_str_mv Universidad Nacional de Colombia - Sede Medellín
institution Universidad Nacional de Colombia
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spelling Atribución-NoComercial-SinDerivadas 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Durango Restrepo, Diego Luis07c2497f44a59162bd9eac38401b16e2Gil González, Jesús Humbertod99077979ca66dbb686a602463e05612Valencia Cossio, Sebastián43d2e412f036a0e06bb8b59f128b4f722024-02-05T21:50:21Z2024-02-05T21:50:21Z2023-01-22https://repositorio.unal.edu.co/handle/unal/85629Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/Ilustraciones, fotosLas enfermedades protozoarias causadas por Trypanosoma cruzii y Leishmania panamensis, son de amplio interés debido a los altos índices de contagios y de muertes que generan alrededor del mundo, prevaleciendo en América latina, Asia y África. Por lo tanto, es imperioso buscar nuevos compuestos como alternativa terapéutica que sirvan como nuevas estrategias eficientes, de fácil acceso, baja resistencia y pocos efectos secundarios en el tratamiento de infecciones protozoarias. Las cumarinas y las chalconas son metabolitos secundarios producidos por las plantas, los cuales han demostrado poseer una gran variedad de actividades farmacológicas. Se ha encontrado que poseen propiedades antiinflamatorias, antibacterianas, antitrombóticas, anticancerígenas, antiAlzheimer, antidiabéticas y antivirales etc. Igualmente han demostrado poseer actividad antiprotozoaria, lo cual genera un posicionamiento importante de estas moléculas en la lucha contra estos parásitos. Las cumarinas y chalconas son dos clases importantes de compuestos bioactivos, que han sido ampliamente estudiados en el área de la química medicinal. Estos compuestos se pueden obtener en el laboratorio por medio de síntesis química y han evidenciado de manera individual o mediante la formación de híbridos, que poseen potencial in vitro contra algunos protozoos. La formación de híbridos entre cumarinas y chalconas se podría aducir como una posible alternativa farmacológica en el tratamiento de infecciones parasitarias. La síntesis de híbridos entre estos dos compuestos se realizó haciendo uso de manera sucesiva de las reacciones de Knoevenagel y Claisen-Schmidt, respectivamente, para su posterior análisis in vitro de citotoxicidad en células U937 y de actividad en amastigotes de Trypanosoma cruzii y promastigotes de Leishmania braziliensis. Los compuestos se caracterizaron por métodos espectroscópicos modernos (IR, RMN). Basados en las propiedades farmacológicas de los híbridos, se realizó un análisis cualitativo de estructura-actividad y de parámetros farmacológicos.La mayoría de los hibridos poseen actividad antiparasitaria contra T. cruzi y L. braziliensis, y una baja toxicidad en la línea celular U937. Las sustituciones de carácter O-alquilo y OH- favorecen en buena medida la actividad inhibitoria. La gran mayoría de los hibridos poseen un perfil farmacológico adecuado; el hibrido H25 exhibió resultados similares al Benznidazol, lo cual lo destaca como un compuesto con potencial para el desarrollo farmacológico. (texto tomado de la fuente)Protozoan diseases caused by Trypanosoma cruzii and Leishmania panamensis are of broad interest due to the high rates of infections and deaths they generate around the world, prevailing in Latin America, Asia and Africa. Therefore, it is imperative to search for new compounds as a therapeutic alternative that serve as new efficient strategies, easy access, low resistance and few side effects in the treatment of protozoan infections. Coumarins and chalcones are secondary metabolites produced by plants, which have been shown to have a wide variety of pharmacological activities. It has been found that they have antiinflammatory, antibacterial, antithrombotic, anticancer, antiAlzheimer's, antidiabetic and antiviral properties, etc. They have also been shown to have antiprotozoal activity, which generates an important position for these molecules in the fight against these parasites. Coumarins and chalcones are two important classes of bioactive compounds, which have been widely studied in the area of medicinal chemistry. These compounds can be obtained in the laboratory through chemical synthesis and have shown, individually or through the formation of hybrids, that they have in vitro potential against some protozoa. The formation of hybrids between coumarins and chalcones could be argued as a possible pharmacological alternative in the treatment of parasitic infections. The synthesis of hybrids between these two compounds was carried out successively using the Knoevenagel and Claisen-Schmidt reactions, respectively, for subsequent in vitro analysis of cytotoxicity in U937 cells and activity in Trypanosoma cruzii amastigotes and Leishmania promastigotes. braziliensis. The compounds were characterized by modern spectroscopic methods (IR, NMR). Based on the pharmacological properties of the hybrids, a qualitative analysis of structure-activity and pharmacological parameters was carried out. Most of the hybrids have antiparasitic activity against T. cruzi and L. braziliensis, and low toxicity in the U937 cell line. Substitutions of O-alkyl and OH- character greatly favor the inhibitory activity. The vast majority of hybrids have an adequate pharmacological profile; Hybrid H25 exhibited similar results to Benznidazole, which highlights it as a compound with potential for pharmacological development.MaestríaMagíster en Ciencias - QuímicaÁrea Curricular en Ciencias Naturales149 páginasapplication/pdfspaUniversidad Nacional de ColombiaMedellín - Ciencias - Maestría en Ciencias - QuímicaFacultad de Ciencias Exactas y NaturalesMedellín, ColombiaUniversidad Nacional de Colombia - Sede Medellín540 - Química y ciencias afinesMedicina tropicalEnfermedades parasitariasInfecciones por protozoariosCumarinasAgentes antiparasitariosTrypanosoma cruziiLeishmaniasisT. cruziL. braziliensisActividad biológicaHíbridosCumarinasChalconasLeishmaniasis cutáneaChalconaSíntesis de híbridos cumarina-chalcona y evaluación de la actividad antiparasitaria in vitroSynthesis of coumarin-chalcone hybrids and evaluation of antiparasitic activity in vitroTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMLaReferencia(1) Organizacion Mundial de la Salud (OMS). 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S. 4-Nitrobenzoylcoumarin Potentiates the Antiparasitic, Anti-Inflammatory and Cardioprotective Effects of Benznidazole in a Murine Model of Acute Trypanosoma Cruzi Infection. Acta Trop. 2022, 228. https://doi.org/10.1016/J.ACTATROPICA.2022.106314.(58) Rodríguez-Hernández, K. D.; Martínez, I.; Reyes-Chilpa, R.; Espinoza, B. Mammea Type Coumarins Isolated from Calophyllum Brasiliense Induced Apoptotic Cell Death of Trypanosoma Cruzi through Mitochondrial Dysfunction, ROS Production and Cell Cycle Alterations. Bioorg. Chem. 2020, 100, 103894. https://doi.org/10.1016/J.BIOORG.2020.103894.(59) Silva, L. G.; Gomes, K. S.; Costa-Silva, T. A.; Romanelli, M. M.; Tempone, A. G.; Sartorelli, P.; Lago, J. H. G. Calanolides E1 and E2, Two Related Coumarins from Calophyllum Brasiliense Cambess. 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