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

Jiru Wu; Xiaodan Li; Xingchen Guo; Zhongbin Cheng; Junjun Meng; Wei Cheng; Wenhan Lin

doi:10.1016/j.bioorg.2020.104423

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. Epub 2020 Oct 24.

Authors

Jiru Wu¹, Xiaodan Li¹, Xingchen Guo¹, Zhongbin Cheng², Junjun Meng¹, Wei Cheng³, Wenhan Lin⁴

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: chengwei@bjmu.edu.cn.
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: whlin@bjmu.edu.cn.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anthozoa
Antiviral Agents / chemistry
Antiviral Agents / isolation & purification
Antiviral Agents / pharmacology*
Cell Line, Tumor
Diterpenes / chemistry
Diterpenes / isolation & purification
Diterpenes / pharmacology*
Dose-Response Relationship, Drug
Hepatitis B virus / drug effects*
Hepatitis B virus / genetics
Humans
Microbial Sensitivity Tests
Molecular Structure
Structure-Activity Relationship

Substances

Antiviral Agents
Diterpenes