Diseño racional y síntesis de derivados heterocíclicos azufrados y nitrogenados con potencial actividad farmacológica sobre canales iónicos reguladores de las señales nerviosas

dc.contributorOrozco Lopez, Fabian
dc.contributorGrupo de Estudios en Síntesis y Aplicaciones de Compuestos Heterocíclicos (Gesach)
dc.contributorChristian Becerra [0000000296623813]
dc.contributorBECERRA RIVAS, CHRISTIAN ALONSO [0001535835]
dc.contributorChristian Alonso Becerra [Christian-Becerra]
dc.contributorChristian Alonso Becerra Rivas [AJsN-F7-D4NJlHWfvCzFFoYK3QhTUbFz5pzpo46E8Bsiin981m6tOiF4UK2jLdZXDlh_SOl32nxOMRzvYaQkQpr3QZc9GaRN6A]
dc.creatorBecerra Rivas, Christian Alonso
dc.date.accessioned2023-07-28T14:19:03Z
dc.date.accessioned2023-08-25T14:14:21Z
dc.date.available2023-07-28T14:19:03Z
dc.date.available2023-08-25T14:14:21Z
dc.date.created2023-07-28T14:19:03Z
dc.date.issued2023
dc.identifierhttps://repositorio.unal.edu.co/handle/unal/84352
dc.identifierUniversidad Nacional de Colombia
dc.identifierRepositorio Institucional Universidad Nacional de Colombia
dc.identifierhttps://repositorio.unal.edu.co/
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8427072
dc.description.abstractLos canales iónicos han despertado recientemente el interés de estudio desde la farmacología dada su potencial aplicación como dianas terapéuticas en el tratamiento de diversas patologías. En esta medida se planteó una biblioteca de compuestos de núcleo heterocíclico pirazólico, tiazolidinónico, tiazepínico y pirimidínico que pudieran interactuar con dianas moleculares de esta familia de proteínas; resultando de especial interés para este trabajo el receptor GABAA y el canal de sodio dependiente de voltaje NaV1.7. Dicha biblioteca se sometió a un proceso de cribado mediante docking molecular usando 3 programas (AutoDock4, AutoDock-VINA y DOCK6), determinación in silico de los descriptores moleculares de biodisponibilidad de Lipinski (ADME) y predicción de las propiedades toxicológicas, seleccionando los prototipos más promisorios y llevándolos a la fase de síntesis donde se estudiaron también las condiciones óptimas, así como sutilezas estructurales y de reactividad orientadas al mejoramiento de los procesos químicos que permitieron obtener con buenos rendimientos, 4 series de compuestos con un alto perfil promisorio en modulación de los canales iónicos diana para el tratamiento de enfermedades derivadas de una desregulación autonómica de las señales nerviosas. Además del nuevo conocimiento obtenido sobre los aspectos estructurales, cinéticos y termodinámicos pertinentes para la síntesis de las moléculas objetivo de interés para este estudio.
dc.description.abstractIon channels have recently aroused study interest from pharmacology, given their potential usage as therapeutic targets in the treatment of diverse pathologies. To this purpose, a library of compounds with heterocyclic nucleus such as pyrazole, thiazolidine, thiazepine and pyrimidine was proposed, so that they could interact with molecular targets of this family of proteins; resulting especially interesting for the purpose of this work, GABA-A receptor and voltage gated sodium channel NaV1.7. Mentioned library was subjected to a screening process by molecular docking using three programs (AutoDock4, AutoDock-VINA, and DOCK6), in silico calculus of Lipinski bioavailability descriptors (ADME) and prediction of toxicological properties, selecting the most promising prototypes and taking them to synthesis phase, where optimal conditions as well as structural and reactivity subtleties were studied, aiming for the improvement of the chemical processes that allowed to obtain with good yields, four series of compounds with high promising profile in modulation of the target ion channels for the treatment of diseases related from autonomic deregulation of nerve signals. Besides of new knowledge acquired about the structural, kinetic and thermodynamic aspects related with the synthesis of target molecules interesting for the purposes of this work.
dc.languagespa
dc.publisherUniversidad Nacional de Colombia
dc.publisherBogotá - Ciencias - Doctorado en Ciencias - Química
dc.publisherFacultad de Ciencias
dc.publisherBogotá, Colombia
dc.publisherUniversidad Nacional de Colombia - Sede Bogotá
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dc.rightsAtribución-NoComercial 4.0 Internacional
dc.rightshttp://creativecommons.org/licenses/by-nc/4.0/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleDiseño racional y síntesis de derivados heterocíclicos azufrados y nitrogenados con potencial actividad farmacológica sobre canales iónicos reguladores de las señales nerviosas
dc.typeTrabajo de grado - Doctorado


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