Briarane-type diterpenoids from a gorgonian coral Ellisella sp. with anti-HBV activities

  • Bioorg Chem. 2020 Dec;105:104423. doi: 10.1016/j.bioorg.2020.104423.
Jiru Wu  1 ,  Xiaodan Li  1 ,  Xingchen Guo  1 ,  Zhongbin Cheng  2 ,  Junjun Meng  1 ,  Wei Cheng  3 ,  Wenhan Lin  4
Affiliations
  • 1. State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, PR China.
  • 2. School of Pharmacy, Henan University, Kaifeng 475004, PR China.
  • 3. State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, PR China. Electronic address: [email protected].
  • 4. State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, PR China; Institute of Ocean Research, Peking University, Beijing, PR China. Electronic address: [email protected].
PMID: 33160223 DOI: 10.1016/j.bioorg.2020.104423
Abstract

Chemical investigation of a gorgonian coral Ellisella sp. resulted in the isolation of 12 briarane-type Diterpenoids, including eight new congeners namely ellisellolides A-H (1-8). Their structures were determined by extensive spectroscopic analysis, aided the calculated ECD data to support the configurational assignment. All compounds were evaluated for the in vitro anti-HBV activities in HepAD38 cell line, while preliminary analyses of the structure-activity relationship demonstrated that junceellolide C featured an 3E,5(16)-diene and a chlorine-substitution at C-6 is the most active congener. Junceellolide C exhibited efficient reduction against the HBV DNA, HBV RNA and HBeAg production with a dose-dependent manner. It also significantly reduced the HBV cccDNA replenishment and promoted the existed HBV cccDNA degradation. These findings suggest junceellolide C to be a transcription inhibitor of cccDNA and a promising lead for the development of new anti-HBV agent.

Keywords
Anti-HBV activities; Briarane diterpenoids; Ellisella sp.; Ellisellolides A-H; Gorgonian coral; Structural elucidation.
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