Design, synthesis and biological evaluation of novel methyl selenoesters as antiproliferative and cytotoxic agents
Palabras clave : 
Química orgánica
Diseño, síntesis y estudio de nuevos fármacos
Materias Investigacion::Química::Química orgánica
Fecha de publicación: 
6-feb-2019
Fecha de la defensa: 
14-dic-2018
Cita: 
DÍAZ ARGELICH, Nuria. "Design, synthesis and biological evaluation of novel methyl selenoesters as antiproliferative and cytotoxic agents". Sanmartín, M. C. y Palop ,J. A. (dirs.). Tesis doctoral. Universidad de Navarra, 2018.
Resumen
In this work, an innovative series of methylselenoesters as methylselenol precursors has been designed, synthesized and evaluated. The chemical characteristics of the carbonyl-selenium bond allow a nucleophilic attack that can render methylselenol, a key molecule in selenium biological activity. The scaffolds were chosen among carboaromatic and heteroaromatic rings with reported antitumoral activity to improve the action of methylselenol and to provide enough chemical variety to modulate the strength of the carbonyl-selenium bond, therefore hindering or facilitating a nucleophilic attack, i.e., by water. The release rate of methylselenol was determined, as well as the cytotoxic activity of the compounds against a panel of cancer cell lines. The leader compounds were further investigated to determine their mechanism of action as entosis inducers, which had not been previously described. In addition, other selenium compounds were evaluated. Methylseleninic acid and selenite were tested in a leukemic cell line to explore their genome-wide epigenetic effect. Furthermore, these compounds were also evaluated as immune regulators in the context of ovarian cancer.

Ficheros en este registro:
Fichero: 
Tesis_DiazArgelich18.pdf
Descripción: 
Tamaño: 
14,97 MB
Formato: 
Adobe PDF


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