Synthesis of benzopyran derivatives as PPARα and/or PPARγ activators
We describe the synthesis of 26 compounds, small polycerasoidol analogs, that are Lipinski’s rule-of-five compliant. In order to confirm key structural features to activate PPARα and/or PPARγ, we have adopted structural modifications in the following parts: (i) the benzopyran core (hydrophobic nucle...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Artículo |
| Language: | Inglés |
| Published: |
Elsevier
2020
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| Subjects: | |
| Online Access: | http://hdl.handle.net/20.500.11939/6461 https://www.sciencedirect.com/science/article/pii/S0968089619316505 |
| _version_ | 1855492088654725120 |
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| author | Bermejo, Almudena Barrachina, Isabel El Aouad, Noureddine Franck, Xavier Chahboune, Nadia Andreu, Inmaculada Figadère, Bruno Vila, Laura hennuyer, Nathalie Staels, Bart Dacquet, Catherine Caignard, Daniel H. Sanz, María-Jesús Cortés, Diego Cabedo, Nuria |
| author_browse | Andreu, Inmaculada Barrachina, Isabel Bermejo, Almudena Cabedo, Nuria Caignard, Daniel H. Chahboune, Nadia Cortés, Diego Dacquet, Catherine El Aouad, Noureddine Figadère, Bruno Franck, Xavier Sanz, María-Jesús Staels, Bart Vila, Laura hennuyer, Nathalie |
| author_facet | Bermejo, Almudena Barrachina, Isabel El Aouad, Noureddine Franck, Xavier Chahboune, Nadia Andreu, Inmaculada Figadère, Bruno Vila, Laura hennuyer, Nathalie Staels, Bart Dacquet, Catherine Caignard, Daniel H. Sanz, María-Jesús Cortés, Diego Cabedo, Nuria |
| author_sort | Bermejo, Almudena |
| collection | ReDivia |
| description | We describe the synthesis of 26 compounds, small polycerasoidol analogs, that are Lipinski’s rule-of-five compliant. In order to confirm key structural features to activate PPARα and/or PPARγ, we have adopted structural modifications in the following parts: (i) the benzopyran core (hydrophobic nucleus) by benzopyran-4-one, dihydrobenzopyran or benzopyran-4-ol; (ii) the side chain at 2-position by shortening to C3, C4 and C5-carbons versus C-9-carbons of polycerasoidol; (iii) the carboxylic group (polar head) by oxygenated groups (hydroxyl, acetoxy, epoxide, ester, aldehyde) or non-oxygenated motifs (allyl and alkyl). Benzopyran-4-ones 6, 12, 13 and 17 as well as dihydrobenzopyrans 22, 24 and 25 were able to activate hPPARα, whereas benzopyran-4-one (7) with C5-carbons in the side chain exhibited hPPARγ agonism. According to our previous docking studies, SAR confirm that the hydrophobic nucleus (benzopyran-4-one or dihydrobenzopyran) is essential to activate PPARα and/or PPARγ, and the flexible linker (side alkyl chain) should containg at least C5-carbon atoms to activate PPARγ. By contrast, the polar head (“carboxylic group”) tolerated several oxygenated groups but also non-oxygenated motifs. Taking into account these key structural features, small polycerasoidol analogs might provide potential active molecules useful in the treatment of dyslipidemia and/or type 2 diabetes. |
| format | Artículo |
| id | ReDivia6461 |
| institution | Instituto Valenciano de Investigaciones Agrarias (IVIA) |
| language | Inglés |
| publishDate | 2020 |
| publishDateRange | 2020 |
| publishDateSort | 2020 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| record_format | dspace |
| spelling | ReDivia64612025-04-25T14:47:09Z Synthesis of benzopyran derivatives as PPARα and/or PPARγ activators Bermejo, Almudena Barrachina, Isabel El Aouad, Noureddine Franck, Xavier Chahboune, Nadia Andreu, Inmaculada Figadère, Bruno Vila, Laura hennuyer, Nathalie Staels, Bart Dacquet, Catherine Caignard, Daniel H. Sanz, María-Jesús Cortés, Diego Cabedo, Nuria Polycerasoidol PPARα agonism PPARγ agonism F60 Plant physiology and biochemistry Benzopyrene We describe the synthesis of 26 compounds, small polycerasoidol analogs, that are Lipinski’s rule-of-five compliant. In order to confirm key structural features to activate PPARα and/or PPARγ, we have adopted structural modifications in the following parts: (i) the benzopyran core (hydrophobic nucleus) by benzopyran-4-one, dihydrobenzopyran or benzopyran-4-ol; (ii) the side chain at 2-position by shortening to C3, C4 and C5-carbons versus C-9-carbons of polycerasoidol; (iii) the carboxylic group (polar head) by oxygenated groups (hydroxyl, acetoxy, epoxide, ester, aldehyde) or non-oxygenated motifs (allyl and alkyl). Benzopyran-4-ones 6, 12, 13 and 17 as well as dihydrobenzopyrans 22, 24 and 25 were able to activate hPPARα, whereas benzopyran-4-one (7) with C5-carbons in the side chain exhibited hPPARγ agonism. According to our previous docking studies, SAR confirm that the hydrophobic nucleus (benzopyran-4-one or dihydrobenzopyran) is essential to activate PPARα and/or PPARγ, and the flexible linker (side alkyl chain) should containg at least C5-carbon atoms to activate PPARγ. By contrast, the polar head (“carboxylic group”) tolerated several oxygenated groups but also non-oxygenated motifs. Taking into account these key structural features, small polycerasoidol analogs might provide potential active molecules useful in the treatment of dyslipidemia and/or type 2 diabetes. 2020-05-25T17:14:10Z 2020-05-25T17:14:10Z 2019 article draft Bermejo, A., Barrachina, I., El Aouad, N., Franck, X., Chahboune, N., Andreu, I., ... & Dacquet, C. (2019). Synthesis of benzopyran derivatives as PPARα and/or PPARγ activators. Bioorganic & medicinal chemistry, 27(24), 115162. 0968-0896 http://hdl.handle.net/20.500.11939/6461 10.1016/j.bmc.2019.115162 https://www.sciencedirect.com/science/article/pii/S0968089619316505 en Atribución-NoComercial-SinDerivadas 3.0 España http://creativecommons.org/licenses/by-nc-nd/3.0/es/ Elsevier electronico |
| spellingShingle | Polycerasoidol PPARα agonism PPARγ agonism F60 Plant physiology and biochemistry Benzopyrene Bermejo, Almudena Barrachina, Isabel El Aouad, Noureddine Franck, Xavier Chahboune, Nadia Andreu, Inmaculada Figadère, Bruno Vila, Laura hennuyer, Nathalie Staels, Bart Dacquet, Catherine Caignard, Daniel H. Sanz, María-Jesús Cortés, Diego Cabedo, Nuria Synthesis of benzopyran derivatives as PPARα and/or PPARγ activators |
| title | Synthesis of benzopyran derivatives as PPARα and/or PPARγ activators |
| title_full | Synthesis of benzopyran derivatives as PPARα and/or PPARγ activators |
| title_fullStr | Synthesis of benzopyran derivatives as PPARα and/or PPARγ activators |
| title_full_unstemmed | Synthesis of benzopyran derivatives as PPARα and/or PPARγ activators |
| title_short | Synthesis of benzopyran derivatives as PPARα and/or PPARγ activators |
| title_sort | synthesis of benzopyran derivatives as pparα and or pparγ activators |
| topic | Polycerasoidol PPARα agonism PPARγ agonism F60 Plant physiology and biochemistry Benzopyrene |
| url | http://hdl.handle.net/20.500.11939/6461 https://www.sciencedirect.com/science/article/pii/S0968089619316505 |
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