{"id":106952,"date":"2018-03-11T10:31:05","date_gmt":"2018-03-11T10:31:05","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/desarrollo-de-nuevos-inhibidores-de-la-enzima-lipasa-de-monoacilgliceridos-mgl-development-of-new-inhibitors-of-the-enzyme-monoacylglycerol-lipase-mgl\/"},"modified":"2018-03-11T10:31:05","modified_gmt":"2018-03-11T10:31:05","slug":"desarrollo-de-nuevos-inhibidores-de-la-enzima-lipasa-de-monoacilgliceridos-mgl-development-of-new-inhibitors-of-the-enzyme-monoacylglycerol-lipase-mgl","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/quimica\/desarrollo-de-nuevos-inhibidores-de-la-enzima-lipasa-de-monoacilgliceridos-mgl-development-of-new-inhibitors-of-the-enzyme-monoacylglycerol-lipase-mgl\/","title":{"rendered":"Desarrollo de nuevos inhibidores de la enzima lipasa de monoacilglic\u00e9ridos (mgl)\/\/ development of new inhibitors of the enzyme monoacylglycerol lipase (mgl)"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Jos\u00e9 Antonio Cisneros Trigo <\/strong><\/h2>\n<p>Desarrollo de nuevos inhibidores de la enzima lipasa de monoacilglic\u00e9ridos (mgl) los endocannabinoides constituyen una clase de mensajeros lip\u00eddicos que modulan un amplio espectro de procesos fisiol\u00f3gicos en el sistema nervioso central y en la perife ria, siendo la n-araquidonoiletanolamina (anandamida, aea) y el 2-araquidonoilglicerol (2-ag) los m\u00e1s importantes. Ambos endocannabinoides exhiben funciones antinociceptivas y neuroprotectoras, est\u00e1n implicados en el comportamiento alimenticio y regu lan tanto el crecimiento como la capacidad invasiva de determinados tipos de tumores. La implicaci\u00f3n de 2-ag en estas patolog\u00edas abre la puerta a la posibilidad de nuevas aproximaciones terap\u00e9uticas basadas en la manipulaci\u00f3n de las enzimas implicada s en su metabolismo. En este sentido, se ha postulado la enzima lipasa de monoacilglic\u00e9ridos (mgl) como la responsable de la degradaci\u00f3n in vivo de 2-ag por lo que la inhibici\u00f3n de esta enzima ha surgido como una de las estrategias m\u00e1s interesantes y  con mayor potencial terap\u00e9utico. en este contexto, dado que al principio de este proyecto no se conoc\u00eda la estructura tridimensional de esta enzima y en ausencia de un inhibidor potente y selectivo, nos basamos en la estructura del sustrato end\u00f3geno  de la mgl, el 2-ag. As\u00ed, hemos dise\u00f1ado y sintetizado una serie de compuestos de estructura general i en la que se ha llevado a cabo un barrido estructural sistem\u00e1tico variando la cadena de \u00e1cido araquid\u00f3nico, sustituyendo el fragmento de glicerol p or diversos heterociclos oxigenados y modificando los espaciadores entre ambas subunidades. Para todos los compuestos sintetizados se ha determinado su capacidad para inhibir la enzima mgl as\u00ed como su selectividad sobre la enzima hidrolasa de amidas de \u00e1cidos grasos (faah), responsable de la degradaci\u00f3n de aea. Por \u00faltimo, los inhibidores \u00f3ptimos se han empleado en diferentes sistemas in vitro con el fin de obtener informaci\u00f3n sobre las enzimas implicadas en la degradaci\u00f3n de 2-ag y establecer s u potencial terap\u00e9utico en un modelo de neuroprotecci\u00f3n. en una primera serie, el estudio de relaci\u00f3n estructura-actividad (sar) permiti\u00f3 seleccionar las subunidades heteroc\u00edclicas de oxirano  y tetrahidropirano, siendo los derivados de \u00e1cido araquid \u00f3nico ucm162 [(5z,8z,11z,14z)-icosa-5,8,11,14-tetraenoato de (\u00c2\u00b1)-oxiran-2-ilmetilo] y ucm505 [(5z,8z,11z,14z)-icosa-5,8,11,14-tetraenoato de (\u00c2\u00b1)-tetrahidro-2h-piran-2-ilmetilo] los que mostraron el mejor perfil in vitro, con unos valores de ci50 para<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Desarrollo de nuevos inhibidores de la enzima lipasa de monoacilglic\u00e9ridos (mgl)\/\/ development of new inhibitors of the enzyme monoacylglycerol lipase (mgl)<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Desarrollo de nuevos inhibidores de la enzima lipasa de monoacilglic\u00e9ridos (mgl)\/\/ development of new inhibitors of the enzyme monoacylglycerol lipase (mgl) <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Jos\u00e9 Antonio Cisneros Trigo <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Complutense de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 23\/02\/2011<\/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>Silvia Ortega Guti\u00e9rrez<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Miguel angel Sierra rodr\u00edguez <\/li>\n<li>beat Lutz (vocal)<\/li>\n<li>christopher Fowler (vocal)<\/li>\n<li>avelino Trabanco suarez andres (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Jos\u00e9 Antonio Cisneros Trigo Desarrollo de nuevos inhibidores de la enzima lipasa de monoacilglic\u00e9ridos (mgl) los endocannabinoides [&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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