Polycerasoidol, a Natural Prenylated Benzopyran with a Dual PPARα/PPARγ Agonist Activity and Anti-inflammatory Effect
Dual peroxisome proliferator-activated receptor-α/γ (PPARα/γ) agonists regulate both lipid and glucose homeostasis under different metabolic conditions and can exert anti-inflammatory activity. We investigated the potential dual PPARα/γ agonism of prenylated benzopyrans polycerasoidol (1) and polyce...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Artículo |
| Language: | Inglés |
| Published: |
ACS publications
2020
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| Subjects: | |
| Online Access: | http://hdl.handle.net/20.500.11939/6462 https://pubs.acs.org/doi/10.1021/acs.jnatprod.9b00003 |
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| author | Bermejo, Almudena Collado, Aida Barrachina, Isabel Marqués, Patrice El Aouad, Noureddine Franck, Xavier Garibotto, Francisco Dacquet, Catherine Caignard, Daniel H. Suvire, Fernando D. Enriz, Ricardo D. Piqueras, Laura Figadère, Bruno Sanz, María-Jesús Cabedo, Nuria Cortés, Diego |
| author_browse | Barrachina, Isabel Bermejo, Almudena Cabedo, Nuria Caignard, Daniel H. Collado, Aida Cortés, Diego Dacquet, Catherine El Aouad, Noureddine Enriz, Ricardo D. Figadère, Bruno Franck, Xavier Garibotto, Francisco Marqués, Patrice Piqueras, Laura Sanz, María-Jesús Suvire, Fernando D. |
| author_facet | Bermejo, Almudena Collado, Aida Barrachina, Isabel Marqués, Patrice El Aouad, Noureddine Franck, Xavier Garibotto, Francisco Dacquet, Catherine Caignard, Daniel H. Suvire, Fernando D. Enriz, Ricardo D. Piqueras, Laura Figadère, Bruno Sanz, María-Jesús Cabedo, Nuria Cortés, Diego |
| author_sort | Bermejo, Almudena |
| collection | ReDivia |
| description | Dual peroxisome proliferator-activated receptor-α/γ (PPARα/γ) agonists regulate both lipid and glucose homeostasis under different metabolic conditions and can exert anti-inflammatory activity. We investigated the potential dual PPARα/γ agonism of prenylated benzopyrans polycerasoidol (1) and polycerasoidin (2) and their derivatives for novel drug development. Nine semisynthetic derivatives were prepared from the natural polycerasoidol (1) and polycerasoidin (2), which were evaluated for PPARα, -γ, -δ and retinoid X receptor-α activity in transactivation assays. Polycerasoidol (1) exhibited potent dual PPARα/γ agonism and low cytotoxicity. Structure–activity relationship studies revealed that a free phenol group at C-6 and a carboxylic acid at C-9′ were key features for dual PPARα/γ agonism activity. Molecular modeling indicated the relevance of these groups for optimal ligand binding to the PPARα and PPARγ domains. In addition, polycerasoidol (1) exhibited a potent anti-inflammatory effect by inhibiting mononuclear leukocyte adhesion to the dysfunctional endothelium in a concentration-dependent manner via RXRα/PPARγ interactions. Therefore, polycerasoidol (1) can be considered a hit-to-lead molecule for the further development of novel dual PPARα/γ agonists capable of preventing cardiovascular events associated with metabolic disorders. |
| format | Artículo |
| id | ReDivia6462 |
| institution | Instituto Valenciano de Investigaciones Agrarias (IVIA) |
| language | Inglés |
| publishDate | 2020 |
| publishDateRange | 2020 |
| publishDateSort | 2020 |
| publisher | ACS publications |
| publisherStr | ACS publications |
| record_format | dspace |
| spelling | ReDivia64622025-04-25T14:47:09Z Polycerasoidol, a Natural Prenylated Benzopyran with a Dual PPARα/PPARγ Agonist Activity and Anti-inflammatory Effect Bermejo, Almudena Collado, Aida Barrachina, Isabel Marqués, Patrice El Aouad, Noureddine Franck, Xavier Garibotto, Francisco Dacquet, Catherine Caignard, Daniel H. Suvire, Fernando D. Enriz, Ricardo D. Piqueras, Laura Figadère, Bruno Sanz, María-Jesús Cabedo, Nuria Cortés, Diego Reaction products Mixtures F60 Plant physiology and biochemistry Agonists Ketones Cells Dual peroxisome proliferator-activated receptor-α/γ (PPARα/γ) agonists regulate both lipid and glucose homeostasis under different metabolic conditions and can exert anti-inflammatory activity. We investigated the potential dual PPARα/γ agonism of prenylated benzopyrans polycerasoidol (1) and polycerasoidin (2) and their derivatives for novel drug development. Nine semisynthetic derivatives were prepared from the natural polycerasoidol (1) and polycerasoidin (2), which were evaluated for PPARα, -γ, -δ and retinoid X receptor-α activity in transactivation assays. Polycerasoidol (1) exhibited potent dual PPARα/γ agonism and low cytotoxicity. Structure–activity relationship studies revealed that a free phenol group at C-6 and a carboxylic acid at C-9′ were key features for dual PPARα/γ agonism activity. Molecular modeling indicated the relevance of these groups for optimal ligand binding to the PPARα and PPARγ domains. In addition, polycerasoidol (1) exhibited a potent anti-inflammatory effect by inhibiting mononuclear leukocyte adhesion to the dysfunctional endothelium in a concentration-dependent manner via RXRα/PPARγ interactions. Therefore, polycerasoidol (1) can be considered a hit-to-lead molecule for the further development of novel dual PPARα/γ agonists capable of preventing cardiovascular events associated with metabolic disorders. 2020-05-25T17:14:46Z 2020-05-25T17:14:46Z 2019 article draft Bermejo, A., Collado, A., Barrachina, I., Marqués, P., El Aouad, N., Franck, X. et al. (2019). Polycerasoidol, a Natural Prenylated Benzopyran with a Dual PPARα/PPARγ Agonist Activity and Anti-inflammatory Effect. Journal of natural products, 82(7), 1802-1812. 0163-3864 http://hdl.handle.net/20.500.11939/6462 10.1021/acs.jnatprod.9b00003 https://pubs.acs.org/doi/10.1021/acs.jnatprod.9b00003 en Atribución-NoComercial-SinDerivadas 3.0 España http://creativecommons.org/licenses/by-nc-nd/3.0/es/ ACS publications electronico |
| spellingShingle | Reaction products Mixtures F60 Plant physiology and biochemistry Agonists Ketones Cells Bermejo, Almudena Collado, Aida Barrachina, Isabel Marqués, Patrice El Aouad, Noureddine Franck, Xavier Garibotto, Francisco Dacquet, Catherine Caignard, Daniel H. Suvire, Fernando D. Enriz, Ricardo D. Piqueras, Laura Figadère, Bruno Sanz, María-Jesús Cabedo, Nuria Cortés, Diego Polycerasoidol, a Natural Prenylated Benzopyran with a Dual PPARα/PPARγ Agonist Activity and Anti-inflammatory Effect |
| title | Polycerasoidol, a Natural Prenylated Benzopyran with a Dual PPARα/PPARγ Agonist Activity and Anti-inflammatory Effect |
| title_full | Polycerasoidol, a Natural Prenylated Benzopyran with a Dual PPARα/PPARγ Agonist Activity and Anti-inflammatory Effect |
| title_fullStr | Polycerasoidol, a Natural Prenylated Benzopyran with a Dual PPARα/PPARγ Agonist Activity and Anti-inflammatory Effect |
| title_full_unstemmed | Polycerasoidol, a Natural Prenylated Benzopyran with a Dual PPARα/PPARγ Agonist Activity and Anti-inflammatory Effect |
| title_short | Polycerasoidol, a Natural Prenylated Benzopyran with a Dual PPARα/PPARγ Agonist Activity and Anti-inflammatory Effect |
| title_sort | polycerasoidol a natural prenylated benzopyran with a dual pparα pparγ agonist activity and anti inflammatory effect |
| topic | Reaction products Mixtures F60 Plant physiology and biochemistry Agonists Ketones Cells |
| url | http://hdl.handle.net/20.500.11939/6462 https://pubs.acs.org/doi/10.1021/acs.jnatprod.9b00003 |
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