{"id":92198,"date":"2018-03-11T10:11:06","date_gmt":"2018-03-11T10:11:06","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/nucleosidos-como-inhibidores-del-factor-angiogenico-timidina-fosfori-lasa\/"},"modified":"2018-03-11T10:11:06","modified_gmt":"2018-03-11T10:11:06","slug":"nucleosidos-como-inhibidores-del-factor-angiogenico-timidina-fosfori-lasa","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/nucleosidos-como-inhibidores-del-factor-angiogenico-timidina-fosfori-lasa\/","title":{"rendered":"Nucle\u00f3sidos como inhibidores del factor angiog\u00e9nico timidina fosfori  lasa."},"content":{"rendered":"<h2>Tesis doctoral de <strong> Elena Casanova Malpica <\/strong><\/h2>\n<p>Null esta tesis doctoral ha estado centrada en la b\u00fasqueda de nuevos inhibidores de la enzima timidina fosforilasa (factor implicado en el proceso de angiog\u00e9nesis), mediante la s\u00edntesis y evaluaci\u00f3n biol\u00f3gica de compuestos estructuralmente relacionados co n la 5\u00c2\u00bf-o-tritilinosina y la 5\u00c2\u00bf-o-tritiltimidina, inhibidores alost\u00e9ricos de dicha enzima.  as\u00ed, a trav\u00e9s de distintas estrategias sint\u00e9ticas, se han obtenido nucle\u00f3sidos modificados en diferentes posiciones reactivas tanto de la base como del az\u00facar  de inosina y timidina. La evaluaci\u00f3n de los  compuestos sintetizados frente a timidina fosforilasa ha permitido establecer los requisitos estructurales m\u00ednimos para la actividad inhibitoria y mejorar hasta 10 veces la potencia respecto a los compues tos empleados como patr\u00f3n.   por otra parte, se han intentado solventar los problemas de difusi\u00f3n y\/o solubilidad que presenta la 5\u00c2\u00bf-o-tritiltimidina en los ensayos de angiog\u00e9nesis, mediante el uso de una aproximaci\u00f3n prof\u00e1rmaco y a trav\u00e9s de la s\u00ednt esis de diferentes hemisuccinatos y \u00e9steres de valina en la posici\u00f3n 3\u00c2\u00bf de dicho nucle\u00f3sido patr\u00f3n. Algunos de estos compuestos han mostrado una potente actividad antiangiog\u00e9nica.  adem\u00e1s, se ha realizado la s\u00edntesis, elucidaci\u00f3n estructural y an\u00e1lis is conformacional tanto por rmn como por modelizaci\u00f3n molecular de una serie de nucle\u00f3sidos derivados de la 2\u00c2\u00bf,3\u00c2\u00bf-o-isopropilideninosina sustituidos en la posici\u00f3n n7 y con un grupo bencilo en la posici\u00f3n 5\u00c2\u00bf. Estos compuestos muestran una clara restr icci\u00f3n  conformacional en disoluci\u00f3n, que en base a los datos obtenidos, podr\u00eda ser debida a una estabilizaci\u00f3n intramolecular tipo pi-cati\u00f3n,  siendo uno de los pocos ejemplos descritos en la literatura.  para finalizar, se ha puesto a punto un proc edimiento de s\u00edntesis asistida por microondas para la tritilaci\u00f3n selectiva en la posici\u00f3n 5\u00c2\u00bf de derivados de inosina, procedimiento que consigue mejorar considerablemente los rendimientos y reducir los tiempos de reacci\u00f3n respecto a la reacci\u00f3n con calentamiento est\u00e1ndar.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Nucle\u00f3sidos como inhibidores del factor angiog\u00e9nico timidina fosfori  lasa.<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Nucle\u00f3sidos como inhibidores del factor angiog\u00e9nico timidina fosfori  lasa. <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Elena Casanova Malpica <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Complutense de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 13\/03\/2009<\/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>Mar\u00eda Jes\u00fas P\u00e9rez P\u00e9rez<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Antonio  (secretario) Herrera fern\u00e1ndez <\/li>\n<li>  (vocal)<\/li>\n<li>  (vocal)<\/li>\n<li>  (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Elena Casanova Malpica Null esta tesis doctoral ha estado centrada en la b\u00fasqueda de nuevos inhibidores de [&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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