2026-06-14T06:44:27Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/93292025-06-17T13:14:15Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19616

00925njm 22002777a 4500 dc Cuadrado, Irene author Amesty, Ángel author Cedrón, Juan Carlos author Oberti, Juan Carlos author Estévez-Braun, Ana author Hortelano, Sonsoles author de Las Heras, Beatriz author 2018 A series of nine derivatives (2⁻10) were prepared from the diterpene solidagenone (1) and their structures were elucidated by means of spectroscopic studies. Their ability to inhibit inflammatory responses elicited in peritoneal macrophages by TLR ligands was investigated. Compounds 5 and 6 showed significant anti-inflammatory effects, as they inhibited the protein expression of nitric oxide synthase (NOS-2), cyclooxygenase-2 (COX-2), and cytokine production (TNF-α, IL-6, and IL-12) induced by the ligand of TLR4, lipopolysaccharide (LPS), acting at the transcriptional level. Some structure⁻activity relationships were outlined. Compound 5 was selected as a representative compound and molecular mechanisms involved in its biological activity were investigated. Inhibition of NF-κB and p38 signaling seems to be involved in the mechanism of action of compound 5. In addition, this compound also inhibited inflammatory responses mediated by ligands of TLR2 and TLR3 receptors. To rationalize the obtained results, molecular docking and molecular dynamic studies were carried out on TLR4. All these data indicate that solidagenone derivative 5 might be used for the design of new anti-inflammatory agents. Molecules. 2018 Dec 4;23(12). pii: E3197. 10.3390/molecules23123197 1420-3049 1420-3049 Molecules (Basel, Switzerland) 30518153 http://hdl.handle.net/20.500.12105/9329 TLR4 Diterpenes Inflammation Molecular docking Solidagenone derivatives Semisynthesis and Inhibitory Effects of Solidagenone Derivatives on TLR-Mediated Inflammatory Responses