RT Journal Article
T1 Semisynthesis and Inhibitory Effects of Solidagenone Derivatives on TLR-Mediated Inflammatory Responses
A1 Cuadrado Berrocal, Irene
A1 Amesty, Ángel
A1 Cedrón, Juan Carlos
A1 Oberti, Juan Carlos
A1 Estévez-Braun, Ana
A1 Hortelano, Sonsoles
A1 De las Heras Polo, Beatriz
AB 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.
PB MDPI
SN 1420-3049
YR 2018
FD 2018-12-04
LK https://hdl.handle.net/20.500.14352/12718
UL https://hdl.handle.net/20.500.14352/12718
LA eng
NO Ministerio de Economía y Competitividad (MINECO)
NO Instituto de Salud Carlos III/FEDER
NO Gobierno Autónomo de Canarias
DS Docta Complutense
RD 6 abr 2025