Dehydrohispanolone Derivatives Attenuate the Inflammatory Response through the Modulation of Inflammasome Activation
The NLRP3 inflammasome plays a critical role in inflammation-mediated human diseases and represents a promising drug target for novel anti-inflammatory therapies. Hispanolone is a labdane diterpenoid isolated from the aerial parts of Ballota species. This diterpenoid and some derivatives have demons...
| Autores: | , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/17375 |
| Acceso en línea: | http://hdl.handle.net/20.500.12105/17375 |
| Access Level: | acceso abierto |
| Palabra clave: | Animals Diterpenes Humans Inflammasomes Inflammation Molecular Structure NLR Family, Pyrin Domain-Containing 3 Protein Structure-Activity Relationship |
| Sumario: | The NLRP3 inflammasome plays a critical role in inflammation-mediated human diseases and represents a promising drug target for novel anti-inflammatory therapies. Hispanolone is a labdane diterpenoid isolated from the aerial parts of Ballota species. This diterpenoid and some derivatives have demonstrated anti-inflammatory effects in classical inflammatory pathways. In the present study, a series of dehydrohispanolone derivatives (1-19) was synthesized, and their anti-inflammatory activities toward NLRP3 inflammasome activation were evaluated. The structures of the dehydrohispanolone analogues produced were elucidated by NMR spectroscopy and mass spectrometry. Four derivatives significantly inhibited IL-1β secretion, with 15 and 18 being the most active (IC50 = 18.7 and 13.8 μM, respectively). Analysis of IL-1β and caspase-1 expression revealed that the new diterpenoids 15 and 18 are selective inhibitors of the NLRP3 inflammasome, reinforcing the previously demonstrated anti-inflammatory properties of hispanolone derivatives. |
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