2026-06-29T01:20:34Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1188912025-05-23T17:44:49Zcom_20.500.14352_14col_20.500.14352_15

00925njm 22002777a 4500 dc Heras Polo, Beatriz De Las author González Cofrade, Laura author Cuadrado Berrocal, Irene author Oramas-Royo, Sandra author Amesty, Angel author Hortelano, Sonsoles author Estevez-Braun, Ana author 2020 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 González-Cofrade L, Oramas-Royo S, Cuadrado I, Amesty Á, Hortelano S, Estevez-Braun A, et al. Dehydrohispanolone Derivatives Attenuate the Inflammatory Response through the Modulation of Inflammasome Activation. J Nat Prod 2020;83:2155–64. https://doi.org/10.1021/acs.jnatprod.0c00200. 10.1021/acs.jnatprod.0c00200 https://hdl.handle.net/20.500.14352/118891 https://doi.org/10.1021/acs.jnatprod.0c00200 https://pubs.acs.org/journal/jnprdf Dehydrohispanolone derivatives attenuate the inflammatory response through the modulation of inflammasome activation