2. Academic Validation
  3. The First Discovery of Marine Polyoxygenated Cembranolides as Potential Agents for the Treatment of Ulcerative Colitis

The First Discovery of Marine Polyoxygenated Cembranolides as Potential Agents for the Treatment of Ulcerative Colitis

  • J Med Chem. 2024 Jul 25;67(14):12248-12260. doi: 10.1021/acs.jmedchem.4c00950.
Yuan-Yuan Cui 1 2 3,  Yang Jin 2 3,  Ruo-Nan Sun 2 3,  Xue Wang 3,  Cheng-Long Gao 3,  Xiao-Yun Cui 3,  Kai-Xian Chen 2,  Yi-Li Sun 2 3,  Yue-Wei Guo 3 4,  Jia Li 1 2 3 5 6,  Xu-Wen Li 2 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
  • 2 State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 3 Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China.
  • 4 School of Medicine, Shanghai University, Shanghai 200444, China.
  • 5 Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310000, China.
  • 6 Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Guangdong, Zhongshan Tsuihang New District 528400, China.
PMID: 38959374 DOI: 10.1021/acs.jmedchem.4c00950
Abstract

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.

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