Design, synthesis and biological evaluation of novel methyl selenoesters as antiproliferative and cytotoxic agents
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...
| Main Authors: | , , |
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| Format: | info:eu-repo/semantics/doctoralThesis |
| Language: | eng |
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2019
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10171/56406 |
| _version_ | 1793400595101515776 |
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| author | Díaz-Argelich, N. (Nuria) Sanmartin-Grijalba, C. (Carmen) Palop-Cubillo, J.A. (Juan Antonio) |
| author_facet | Díaz-Argelich, N. (Nuria) Sanmartin-Grijalba, C. (Carmen) Palop-Cubillo, J.A. (Juan Antonio) |
| author_sort | Díaz-Argelich, N. (Nuria) |
| collection | DSpace |
| description | 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. |
| format | info:eu-repo/semantics/doctoralThesis |
| id | oai:dadun.unav.edu:10171-56406 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2019 |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-564062020-07-21T01:14:37Z Design, synthesis and biological evaluation of novel methyl selenoesters as antiproliferative and cytotoxic agents Díaz-Argelich, N. (Nuria) Sanmartin-Grijalba, C. (Carmen) Palop-Cubillo, J.A. (Juan Antonio) Química orgánica Diseño, síntesis y estudio de nuevos fármacos Materias Investigacion::Química::Química orgánica 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. 2019-02-06T11:36:17Z 2019-02-06T11:36:17Z 2019-02-06 2018-12-14 info:eu-repo/semantics/doctoralThesis https://hdl.handle.net/10171/56406 eng info:eu-repo/semantics/openAccess application/pdf |
| spellingShingle | Química orgánica Diseño, síntesis y estudio de nuevos fármacos Materias Investigacion::Química::Química orgánica Díaz-Argelich, N. (Nuria) Sanmartin-Grijalba, C. (Carmen) Palop-Cubillo, J.A. (Juan Antonio) Design, synthesis and biological evaluation of novel methyl selenoesters as antiproliferative and cytotoxic agents |
| title | Design, synthesis and biological evaluation of novel methyl selenoesters as antiproliferative and cytotoxic agents |
| title_full | Design, synthesis and biological evaluation of novel methyl selenoesters as antiproliferative and cytotoxic agents |
| title_fullStr | Design, synthesis and biological evaluation of novel methyl selenoesters as antiproliferative and cytotoxic agents |
| title_full_unstemmed | Design, synthesis and biological evaluation of novel methyl selenoesters as antiproliferative and cytotoxic agents |
| title_short | Design, synthesis and biological evaluation of novel methyl selenoesters as antiproliferative and cytotoxic agents |
| title_sort | design, synthesis and biological evaluation of novel methyl selenoesters as antiproliferative and cytotoxic agents |
| topic | Química orgánica Diseño, síntesis y estudio de nuevos fármacos Materias Investigacion::Química::Química orgánica |
| url | https://hdl.handle.net/10171/56406 |
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