The First Discovery of Marine Polyoxygenated Cembranolides as Potential Agents for the Treatment of Ulcerative Colitis.
Yuan-Yuan CuiYang JinRuo-Nan SunXue WangCheng-Long GaoXiao-Yun CuiKai-Xian ChenYi-Li SunYue-Wei GuoJia LiXu-Wen LiPublished in: Journal of medicinal chemistry (2024)
Cembranolides are characteristic metabolites in marine soft corals, with complex structures and widespread biological activities. However, seldom has an intensive pharmacological study been done for these intriguing marine natural products. In this work, systematic chemical investigation was performed on Sinularia pedunculata by HSQC-based small molecule accurate recognition technology (SMART), resulting in the isolation and identification of 31 cembrane-type diterpenoids, including six new ones. In the bioassay, several compounds showed significant anti-inflammatory activities on the inhibition of NO production. The structure-activity relationship (SAR) was comprehensively analyzed, and two most bioactive and less toxic compounds 8 and 9 could inhibit inflammation through suppressing NF-κB and MAPK signaling pathways, and reduce the secretion of inflammatory cytokines. In a mouse model of dextran sodium sulfate (DSS)-induced acute colitis, 8 and 9 exhibited good anti-inflammatory effects and the ability to repair the colon epithelium, giving insight into the application of cembranolides as potential ulcerative colitis (UC) agents.
Keyphrases
- ulcerative colitis
- signaling pathway
- small molecule
- pi k akt
- oxidative stress
- structure activity relationship
- mouse model
- anti inflammatory
- high resolution
- induced apoptosis
- protein protein
- epithelial mesenchymal transition
- human health
- ms ms
- risk assessment
- lps induced
- mass spectrometry
- inflammatory response
- cell proliferation
- smoking cessation