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dc.contributor.author
Vettorazzi, Marcela Cristina
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Insuasty, Daniel
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Lima, Santiago
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Gutierrez, Lucas Joel
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Nogueras, Manuel
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Marchal, Antonio
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Abonia, Rodrigo
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Andujar, Sebastian Antonio
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Spiegel, Sarah
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Cobo, Justo
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Enriz, Ricardo Daniel
dc.date.available
2020-11-23T14:45:25Z
dc.date.issued
2020-01
dc.identifier.citation
Vettorazzi, Marcela Cristina; Insuasty, Daniel; Lima, Santiago; Gutierrez, Lucas Joel; Nogueras, Manuel; et al.; Design of new quinolin-2-one-pyrimidine hybrids as sphingosine kinases inhibitors; Academic Press Inc Elsevier Science; Bioorganic Chemistry; 94; 103414; 1-2020; 1-20
dc.identifier.issn
0045-2068
dc.identifier.uri
http://hdl.handle.net/11336/118780
dc.description.abstract
Sphingosine-1-phosphate is now emerging as an important player in cancer, inflammation, autoimmune, neurological and cardiovascular disorders. Abundance evidence in animal and humans cancer models has shown that SphK1 is linked to cancer. Thus, there is a great interest in the development new SphK1 inhibitors as a potential new treatment for cancer. In a search for new SphK1 inhibitors we selected the well-known SKI-II inhibitor as the starting structure and we synthesized a new inhibitor structurally related to SKI-II with a significant but moderate inhibitory effect. In a second approach, based on our molecular modeling results, we designed new structures based on the structure of PF-543, the most potent known SphK1 inhibitor. Using this approach, we report the design, synthesis and biological evaluation of a new series of compounds with inhibitory activity against both SphK1 and SphK2. These new inhibitors were obtained incorporating new connecting chains between their polar heads and hydrophobic tails. On the other hand, the combined techniques of molecular dynamics simulations and QTAIM calculations provided complete and detailed information about the molecular interactions that stabilize the different complexes of these new inhibitors with the active sites of the SphK1. This information will be useful in the design of new SphK inhibitors.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Academic Press Inc Elsevier Science
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Sphingosine kinase 1 inhibitors
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Quinolin-2-one-pyrimidine hybrids
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Synthesis
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Bioassays
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Molecular modelling
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Otras Ciencias Químicas
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Ciencias Químicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Design of new quinolin-2-one-pyrimidine hybrids as sphingosine kinases inhibitors
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-11-18T20:45:34Z
dc.journal.volume
94
dc.journal.number
103414
dc.journal.pagination
1-20
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Vettorazzi, Marcela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
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Fil: Insuasty, Daniel. Universidad de Jaén; España
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Fil: Lima, Santiago. Virginia Commonwealth University School of Medicine; Estados Unidos
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Fil: Gutierrez, Lucas Joel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
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Fil: Nogueras, Manuel. Universidad de Jaén; España
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Fil: Marchal, Antonio. Universidad de Jaén; España
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Fil: Abonia, Rodrigo. Universidad del Valle; Colombia
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Fil: Andujar, Sebastian Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
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Fil: Spiegel, Sarah. Virginia Commonwealth University School of Medicine; Estados Unidos
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Fil: Cobo, Justo. Universidad del Valle; Colombia
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Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
dc.journal.title
Bioorganic Chemistry
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0045206819312362
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.bioorg.2019.103414
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