2026-06-14T03:32:36Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/173762024-09-28T02:05:25Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19616
Repisalud author González-Cofrade, Laura author Green, Jack P author Cuadrado, Irene author Amesty, Ángel author Oramas-Royo, Sandra author Brough, David author Estévez-Braun, Ana author Hortelano, Sonsoles author de Las Heras, Beatriz funder Instituto de Salud Carlos III funder Ministerio de Ciencia, Innovación y Universidades (España) funder Agencia Canaria de Investigación, Innovación y Sociedad de la Información funder Ministerio de Universidades (España) 2024-01-25T19:54:47Z 2024-01-25T19:54:47Z 2023-03 Bioorg Chem. 2023 Mar:132:106362. 10.1016/j.bioorg.2023.106362 1090-2120 Bioorganic chemistry 36657273 http://hdl.handle.net/20.500.12105/17376 Dysregulated inflammasome activity, particularly of the NLRP3 inflammasome, is associated with the development of several inflammatory diseases. The study of molecules directly targeting NLRP3 is an emerging field in the discovery of new therapeutic compounds for the treatment of inflammatory disorders. Friedelane triterpenes are biologically active phytochemicals having a wide range of activities including anti-inflammatory effects. In this work, we evaluated the potential anti-inflammatory activity of phenolic and quinonemethide nor-triterpenes (1-11) isolated from Maytenus retusa and some semisynthetic derivatives (12-16) through inhibition of the NLRP3 inflammasome in macrophages. Among them, we found that triterpenes 6 and 14 were the most potent, showing markedly reduced caspase-1 activity, IL-1β secretion (IC50 = 1.15 µM and 0.19 µM, respectively), and pyroptosis (IC50 = 2.21 µM and 0.13 µM, respectively). Further characterization confirmed their selective inhibition of NLRP3 inflammasome in both canonical and non-canonical activation pathways with no effects on AIM2 or NLRC4 inflammasome activation. eng Nor-friedelane triterpenes Maytenus retusa NLRP3 inflammasome ASC Pyroptosis IL-1β Macrophages Phenolic and quinone methide nor-triterpenes as selective NLRP3 inflammasome inhibitors research article 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 URL https://repisalud.isciii.es/bitstreams/aeeb4a9e-a46c-4d6e-8c59-9462ad4a84a1/download File MD5 560a5695d04ca8bc9bbd756843e47150 2431164 application/pdf PhenolicQuinoneMethideNor-triterpenes_2023.pdf URL https://repisalud.isciii.es/bitstreams/c4cb5b74-383a-4089-8bef-985a90c5d1f1/download File MD5 b82c578236444c047f5df4873aba35f5 67804 text/plain PhenolicQuinoneMethideNor-triterpenes_2023.pdf.txt