Diseño racional, síntesis y caracterización de híbridos quiméricos de heterociclos nitrogenados y azufrados como potenciales agentes antifúngicos

ilustraciones, gráficas, tablas

Autores:: Páez Ramos, German Ricardo

Tipo de recurso:

Fecha de publicación:: 2023

Institución:: Universidad Nacional de Colombia

Repositorio:: Universidad Nacional de Colombia

Idioma:: spa

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dc.title.spa.fl_str_mv	Diseño racional, síntesis y caracterización de híbridos quiméricos de heterociclos nitrogenados y azufrados como potenciales agentes antifúngicos
dc.title.translated.eng.fl_str_mv	Rational design, synthesis and characterization of chimeric hybrids of nitrogenous and sulfur heterocycles as potential antifungal agents
title	Diseño racional, síntesis y caracterización de híbridos quiméricos de heterociclos nitrogenados y azufrados como potenciales agentes antifúngicos
spellingShingle	Diseño racional, síntesis y caracterización de híbridos quiméricos de heterociclos nitrogenados y azufrados como potenciales agentes antifúngicos 610 - Medicina y salud::615 - Farmacología y terapéutica Antifúngicos Infecciones Fúngicas Invasoras Antifungal Agents Invasive Fungal Infections Antifúngico Acoplamiento molecular Pirimidinas Tiazolidonas Síntesis de heterociclos Antifungal Molecular docking Pyrimidines Thiazolidones
title_short	Diseño racional, síntesis y caracterización de híbridos quiméricos de heterociclos nitrogenados y azufrados como potenciales agentes antifúngicos
title_full	Diseño racional, síntesis y caracterización de híbridos quiméricos de heterociclos nitrogenados y azufrados como potenciales agentes antifúngicos
title_fullStr	Diseño racional, síntesis y caracterización de híbridos quiméricos de heterociclos nitrogenados y azufrados como potenciales agentes antifúngicos
title_full_unstemmed	Diseño racional, síntesis y caracterización de híbridos quiméricos de heterociclos nitrogenados y azufrados como potenciales agentes antifúngicos
title_sort	Diseño racional, síntesis y caracterización de híbridos quiméricos de heterociclos nitrogenados y azufrados como potenciales agentes antifúngicos
dc.creator.fl_str_mv	Páez Ramos, German Ricardo
dc.contributor.advisor.none.fl_str_mv	Orozco López, Fabián
dc.contributor.author.none.fl_str_mv	Páez Ramos, German Ricardo
dc.contributor.researchgroup.spa.fl_str_mv	Grupo de Estudios en Síntesis y Aplicaciones de Compuestos Heterocíclicos (Gesach)
dc.subject.ddc.spa.fl_str_mv	610 - Medicina y salud::615 - Farmacología y terapéutica
topic	610 - Medicina y salud::615 - Farmacología y terapéutica Antifúngicos Infecciones Fúngicas Invasoras Antifungal Agents Invasive Fungal Infections Antifúngico Acoplamiento molecular Pirimidinas Tiazolidonas Síntesis de heterociclos Antifungal Molecular docking Pyrimidines Thiazolidones
dc.subject.decs.spa.fl_str_mv	Antifúngicos Infecciones Fúngicas Invasoras
dc.subject.decs.eng.fl_str_mv	Antifungal Agents Invasive Fungal Infections
dc.subject.proposal.spa.fl_str_mv	Antifúngico Acoplamiento molecular Pirimidinas Tiazolidonas Síntesis de heterociclos
dc.subject.proposal.eng.fl_str_mv	Antifungal Molecular docking Pyrimidines Thiazolidones
description	ilustraciones, gráficas, tablas
publishDate	2023
dc.date.accessioned.none.fl_str_mv	2023-05-19T16:50:29Z
dc.date.available.none.fl_str_mv	2023-05-19T16:50:29Z
dc.date.issued.none.fl_str_mv	2023-04-27
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/83834
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/83834 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
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spelling	Atribución-NoComercial-CompartirIgual 4.0 InternacionalDerechos reservados al autor, 2023http://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Orozco López, Fabián016e019176d8a9cdde6d278fa517dbbaPáez Ramos, German Ricardobea645b1c949e53e1df55dff80403861Grupo de Estudios en Síntesis y Aplicaciones de Compuestos Heterocíclicos (Gesach)2023-05-19T16:50:29Z2023-05-19T16:50:29Z2023-04-27https://repositorio.unal.edu.co/handle/unal/83834Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, gráficas, tablasLas altas tasas de morbilidad y mortalidad causadas por infecciones fúngicas están intrínsecamente relacionadas con el desarrollo limitado de antimicóticos y la alta toxicidad de estos compuestos. Las infecciones micóticas son un problema de salud pública en estos tiempos, en vista de que los fármacos utilizados actualmente no son completamente efectivos debido al desarrollo de resistencia, toxicidad y efectos secundarios indeseables. Adicional a esto, la búsqueda de nuevos blancos farmacológicos es un gran desafío, ya que existen muchas similitudes entre las células fúngicas y humanas. Todo lo anterior limita el uso de medicamentos antifúngicos en la medicina actual, por esto es crucial la investigación de nuevos agentes antifúngicos y de nuevas dianas farmacológicas. Para este estudio se implementaron estrategias de acoplamiento molecular, en donde se evaluó mediante programas como AutoDock v.4.2.6, AutoDock Vina v.1.1.2 y Dock v.6.7, el acoplamiento de núcleos heterocíclicos como potenciales inhibidores de la N-miristoil transferasa (NMT) de la C. albicans y la lanosterol 14-α-desmetilasa (CYP51) de la C. albicans como blancos moleculares. Al terminar el cribado virtual, las moléculas fueron ordenadas de acuerdo con su valor de energía de unión al receptor. Con los resultados obtenidos en los tres programas se realizó un consenso usando el método de promedio ponderado de autoescalado (PPAE) para obtener un nuevo valor de puntuación, el cual permitió seleccionar los prototipos más promisorios y llevarlos a la fase de síntesis. Las reacciones de obtención de las moléculas objetivo se plantearon desde los principios de la química verde, por consiguiente, se llevaron a cabo estrategias multicomponente, metodologías de calentamiento no convencional como calentamiento asistido por microondas y ultrasonido, además, se realizaron estudios de disolventes, catalizadores y temperaturas de reacción. (Texto tomado de la fuente)High rates of morbidity and mortality caused by fungal infections are intrinsically related to the limited development of antifungal and their toxicity. Part of the reason is that current drugs are not completely effective due to the development of resistance, and undesirable side effects. In addition to this, searching of new pharmacological targets is a great challenge, considering the similarities between fungal and human cells. All these facts limit the use of antifungal drugs in current medicine; for this reason, investigations of new antifungal agents and pharmacological targets is crucial. In this study, molecular docking strategies were implemented, where the coupling of heterocyclic nuclei as potential inhibitors of N-myristoyl transferase (NMT) from C. albicans and lanosterol 14-α-demethylase (CYP51) from C. albicans as molecular targets. Upon completion of virtual screening, the molecules were ordered according to their receptor binding energy value. With the results obtained in the three programs, a consensus was made using the autoscaling weighted average method (PPAE) in order to obtain a new score value, which allowed selecting the most promising prototypes and taking them to the synthesis phase. The reactions to obtain the target molecules were proposed from the principles of green chemistry, therefore, multicomponent strategies were carried out, non-conventional heating methodologies such as microwave and ultrasound-assisted heating, in addition, studies of the effect of solvents, catalysts and reaction temperatures.MaestríaQuímica de heterociclos134 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Ciencias - QuímicaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y salud::615 - Farmacología y terapéuticaAntifúngicosInfecciones Fúngicas InvasorasAntifungal AgentsInvasive Fungal InfectionsAntifúngicoAcoplamiento molecularPirimidinasTiazolidonasSíntesis de heterociclosAntifungalMolecular dockingPyrimidinesThiazolidonesDiseño racional, síntesis y caracterización de híbridos quiméricos de heterociclos nitrogenados y azufrados como potenciales agentes antifúngicosRational design, synthesis and characterization of chimeric hybrids of nitrogenous and sulfur heterocycles as potential antifungal agentsTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMD. 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Colombiarepositorio_nal@unal.edu.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Diseño racional, síntesis y caracterización de híbridos quiméricos de heterociclos nitrogenados y azufrados como potenciales agentes antifúngicos

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