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Synthesis and Evaluation of Substituted Chroman-4-one and Chromone Derivatives as Sirtuin 2-Selective Inhibitors
[Image: see text] A series of substituted chromone/chroman-4-one derivatives has been synthesized and evaluated as novel inhibitors of SIRT2, an enzyme involved in aging-related diseases, e.g., neurodegenerative disorders. The analogues were efficiently synthesized in a one-step procedure including...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2012
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426190/ https://www.ncbi.nlm.nih.gov/pubmed/22746324 http://dx.doi.org/10.1021/jm3005288 |
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author | Fridén-Saxin, Maria Seifert, Tina Landergren, Marie Rydén Suuronen, Tiina Lahtela-Kakkonen, Maija Jarho, Elina M. Luthman, Kristina |
author_facet | Fridén-Saxin, Maria Seifert, Tina Landergren, Marie Rydén Suuronen, Tiina Lahtela-Kakkonen, Maija Jarho, Elina M. Luthman, Kristina |
author_sort | Fridén-Saxin, Maria |
collection | PubMed |
description | [Image: see text] A series of substituted chromone/chroman-4-one derivatives has been synthesized and evaluated as novel inhibitors of SIRT2, an enzyme involved in aging-related diseases, e.g., neurodegenerative disorders. The analogues were efficiently synthesized in a one-step procedure including a base-mediated aldol condensation using microwave irradiation. The most potent compounds, with inhibitory concentrations in the low micromolar range, were substituted in the 2-, 6-, and 8-positions. Larger, electron-withdrawing substituents in the 6- and 8-positions were favorable. The most potent inhibitor of SIRT2 was 6,8-dibromo-2-pentylchroman-4-one with an IC(50) of 1.5 μM. The synthesized compounds show high selectivity toward SIRT2 over SIRT1 and SIRT3 and represent an important starting point for the development of novel SIRT2 inhibitors. |
format | Online Article Text |
id | pubmed-3426190 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-34261902012-08-24 Synthesis and Evaluation of Substituted Chroman-4-one and Chromone Derivatives as Sirtuin 2-Selective Inhibitors Fridén-Saxin, Maria Seifert, Tina Landergren, Marie Rydén Suuronen, Tiina Lahtela-Kakkonen, Maija Jarho, Elina M. Luthman, Kristina J Med Chem [Image: see text] A series of substituted chromone/chroman-4-one derivatives has been synthesized and evaluated as novel inhibitors of SIRT2, an enzyme involved in aging-related diseases, e.g., neurodegenerative disorders. The analogues were efficiently synthesized in a one-step procedure including a base-mediated aldol condensation using microwave irradiation. The most potent compounds, with inhibitory concentrations in the low micromolar range, were substituted in the 2-, 6-, and 8-positions. Larger, electron-withdrawing substituents in the 6- and 8-positions were favorable. The most potent inhibitor of SIRT2 was 6,8-dibromo-2-pentylchroman-4-one with an IC(50) of 1.5 μM. The synthesized compounds show high selectivity toward SIRT2 over SIRT1 and SIRT3 and represent an important starting point for the development of novel SIRT2 inhibitors. American Chemical Society 2012-07-02 2012-08-23 /pmc/articles/PMC3426190/ /pubmed/22746324 http://dx.doi.org/10.1021/jm3005288 Text en Copyright © 2012 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org. |
spellingShingle | Fridén-Saxin, Maria Seifert, Tina Landergren, Marie Rydén Suuronen, Tiina Lahtela-Kakkonen, Maija Jarho, Elina M. Luthman, Kristina Synthesis and Evaluation of Substituted Chroman-4-one and Chromone Derivatives as Sirtuin 2-Selective Inhibitors |
title | Synthesis and Evaluation
of Substituted Chroman-4-one
and Chromone Derivatives as Sirtuin 2-Selective Inhibitors |
title_full | Synthesis and Evaluation
of Substituted Chroman-4-one
and Chromone Derivatives as Sirtuin 2-Selective Inhibitors |
title_fullStr | Synthesis and Evaluation
of Substituted Chroman-4-one
and Chromone Derivatives as Sirtuin 2-Selective Inhibitors |
title_full_unstemmed | Synthesis and Evaluation
of Substituted Chroman-4-one
and Chromone Derivatives as Sirtuin 2-Selective Inhibitors |
title_short | Synthesis and Evaluation
of Substituted Chroman-4-one
and Chromone Derivatives as Sirtuin 2-Selective Inhibitors |
title_sort | synthesis and evaluation
of substituted chroman-4-one
and chromone derivatives as sirtuin 2-selective inhibitors |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426190/ https://www.ncbi.nlm.nih.gov/pubmed/22746324 http://dx.doi.org/10.1021/jm3005288 |
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