2026-06-14T12:13:08Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/93292025-06-17T13:14:15Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19616
Repisalud
author
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
2020-03-25T12:50:15Z
2020-03-25T12:50:15Z
2018
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
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.
eng
TLR4
Diterpenes
Inflammation
Molecular docking
Solidagenone derivatives
Semisynthesis and Inhibitory Effects of Solidagenone Derivatives on TLR-Mediated Inflammatory Responses
research article
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URL
https://repisalud.isciii.es/bitstreams/af1dd362-1081-44d5-b7d1-ba5d1472e0c1/download
File
MD5
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application/pdf
SemisynthesisAndInhibitoryEffects_2018.pdf
URL
https://repisalud.isciii.es/bitstreams/a3713813-600a-43f3-90a3-fe3478cb3008/download
File
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text/plain
SemisynthesisAndInhibitoryEffects_2018.pdf.txt