Design, synthesis and biological evaluation of novel methyl selenoesters as antiproliferative and cytotoxic agents
- Díaz Argelich, Nuria
- María del Carmen Sanmartín Grijalba Director
- Juan Antonio Palop Cubillo Co-director
Defence university: Universidad de Navarra
Fecha de defensa: 14 December 2018
- Rubén Pío Osés Chair
- Silvia Perez Silanes Secretary
- Alfredo Martínez Ramírez Committee member
- Valentina Gandin Committee member
- Ignacio José Encio Martínez Committee member
Type: Thesis
Abstract
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.