RT Journal Article
T1 Phenolic and quinone methide nor-triterpenes as selective NLRP3 inflammasome inhibitors
A1 González Cofrade, Laura
A1 Green, Jack P
A1 Cuadrado Berrocal, Irene
A1 Amesty, Angel
A1 Oramas-Royo, Sandra
A1 Brough, David
A1 Estevez-Braun, Ana
A1 Hortelano, Sonsoles
A1 Heras Polo, Beatriz De Las
AB 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.
PB Elsevier
YR 2023
FD 2023
LK https://hdl.handle.net/20.500.14352/119539
UL https://hdl.handle.net/20.500.14352/119539
LA eng
NO González-Cofrade L, P. Green J, Cuadrado I, Amesty Á, Oramas-Royo S, David Brough, Estévez-Braun A, Hortelano S, De Las Heras B. Phenolic and quinone methide nor-triterpenes as selective NLRP3 inflammasome inhibitors. Bioorganic Chemistry 2023;132:106362. https://doi.org/10.1016/j.bioorg.2023.106362.
NO Instituto de Salud Carlos III (España)
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Agencia Canaria de Investigación, Innovación y Sociedad de la Información
DS Docta Complutense
RD 29 may 2025