{"id":24800,"date":"2018-03-09T09:15:55","date_gmt":"2018-03-09T09:15:55","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/farmacos-modificadores-de-la-enfermedad-de-alzheimer-124-tiadiazolidin-3-5-dionas-tdzds-primeros-inhibidores-atp-no-competitivos-de-gsk-3beta\/"},"modified":"2018-03-09T09:15:55","modified_gmt":"2018-03-09T09:15:55","slug":"farmacos-modificadores-de-la-enfermedad-de-alzheimer-124-tiadiazolidin-3-5-dionas-tdzds-primeros-inhibidores-atp-no-competitivos-de-gsk-3beta","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/farmacos-modificadores-de-la-enfermedad-de-alzheimer-124-tiadiazolidin-3-5-dionas-tdzds-primeros-inhibidores-atp-no-competitivos-de-gsk-3beta\/","title":{"rendered":"F\u00e1rmacos modificadores de la enfermedad de alzheimer: 1,2,4-tiadiazolidin-3, 5-dionas (tdzds) primeros inhibidores atp -no competitivos de gsk-3beta"},"content":{"rendered":"<h2>Tesis doctoral de <strong> M.mercedes Alonso Gasc\u00f3n <\/strong><\/h2>\n<p>La enfermedad de alzeimer (ea), es actualmente, junto al c\u00e1ncer y las enfermedades cardiovasculares, uno de los principales problemas de salud en los pa\u00edses desarrollados. A pesar de los enormes esfuerzos que se est\u00e1n haciendo en los \u00faltimos a\u00f1os sobre el conocimiento de las bases moleculares de la enfermedad, todava\u00eda hoy no existen f\u00e1rmacos curativos o capaces de detener la enfermedad.  una de las estrategias terap\u00e9uticas que se est\u00e1n estudiando actualmente es evitar la formaci\u00f3n de los ovillos neurofibrilares, una de las lesiones histol\u00f3gicas caracter\u00edsticas de la enfermedad. Este objetivo se puede cumplir impidiendo la hiperfosforilaci\u00f3n de la prote\u00edna tau a trav\u00e9s de inhibidores selectivos del enzima gsk-3beta. En este trabajo se muestran los derivados de 1,2,4-tiadiazolidin-3,5-diona como los primeros inhibidores selectivos de gsk-3beta a nivel micromolar que act\u00faan por un mecanismo atp -no competitivo.  con los buenos resultados biol\u00f3gicos iniciales, se propone la optimizaci\u00f3n de la s\u00edntesis de las tdzds  tanto en soluci\u00f3n como en fase s\u00f3lida. Adem\u00e1s, para valorar la influencia de cada hetero\u00e1tomo del anillo en la actividad biol\u00f3gica, se realizar\u00e1n una serie de modificaciones estructurales, cuya evaluaci\u00f3n biol\u00f3gica frente a gsk-3 permitir\u00e1n establecer una serie de conclusiones sobre la relaci\u00f3n estructura qu\u00edmica-actividad biol\u00f3gica. estas conclusiones sar se corroborar\u00e1n a trav\u00e9s de un modelo comfa que nos permitir\u00e1 proponer la s\u00edntesis de nuevos derivados de tdzd. Con estos datos y junto con las coordenadas cristalogr\u00e1ficas del enzima (publicadas durante la realizaci\u00f3n de esta tesis) mediante un estudio de modelizaci\u00f3n molecular de docking autom\u00e1tico se observar\u00e1 la zona de uni\u00f3n m\u00e1s probable inhibidor-enzima, proponi\u00e9ndose un posible modo de uni\u00f3n irreversible.  adicionalmente se utilizar\u00e1n modelos matem\u00e1ticos de redes neuronales para comprobar la buena biodisponibilidad oral y la<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>F\u00e1rmacos modificadores de la enfermedad de alzheimer: 1,2,4-tiadiazolidin-3, 5-dionas (tdzds) primeros inhibidores atp -no competitivos de gsk-3beta<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 F\u00e1rmacos modificadores de la enfermedad de alzheimer: 1,2,4-tiadiazolidin-3, 5-dionas (tdzds) primeros inhibidores atp -no competitivos de gsk-3beta <\/li>\n<li><strong>Autor:<\/strong>\u00a0 M.mercedes Alonso Gasc\u00f3n <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Aut\u00f3noma de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 16\/07\/2003<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Ana Martinez Gil<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: jose Elguero bertolini <\/li>\n<li>Mar\u00eda  luz Lopez rodriguez (vocal)<\/li>\n<li>Antonio Garc\u00eda Garc\u00eda (vocal)<\/li>\n<li>Javier Mendoza sanz (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de M.mercedes Alonso Gasc\u00f3n La enfermedad de alzeimer (ea), es actualmente, junto al c\u00e1ncer y las enfermedades cardiovasculares, [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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