Heras Polo, Beatriz De LasGonzález Cofrade, LauraCuadrado Berrocal, IreneOramas-Royo, SandraAmesty, AngelHortelano, SonsolesEstevez-Braun, Ana2025-03-212025-03-212020González-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.0c00200https://hdl.handle.net/20.500.14352/118891The 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 derivativesengAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articlehttps://doi.org/10.1021/acs.jnatprod.0c00200https://pubs.acs.org/journal/jnprdfopen access615:54615.31615.01/.03DehydroisohispanoloneInflammasomeInflammationQuímica farmaceúticaFarmacología (Farmacia)3209 Farmacología