Highly oxygenated cembrane diterpenoids from the South China Sea soft coral Sinularia pedunculata and their anti-HBV activities

Abstract

Eleven new highly oxygenated cembrane-type diterpenoids (1−7 and 10−13) and two known analogues (8−9) were isolated from the South China Sea soft coral Sinularia pedunculata. Their structures were determined through extensive spectroscopic analysis, quantum mechanical-nuclear magnetic resonance (QM-NMR) approach and X-ray diffraction analysis. Notably, compounds 3 and 4 were rare cembrane diterpenoids featuring a tetrahydropyran moiety with 5,8-ether and 4,8-ether linkages, respectively, while compounds 4 and 9 inhibited HBV DNA replication with IC₅₀ values of 0.87 and 1.15 μmol·L⁻¹ in HepAD38 cells, respectively. Mechanism investigation suggested that compound 9 accelerated capsid formation without affecting the levels of HBV cccDNA, total RNA, or pgRNA.

Keywords

Soft coral / Sinularia pedunculata / Cembrane diterpenoids / Anti-HBV activity

Funding

This work was supported by the National Key Research and Development Program of China (No. 2021YFF0502400), the Natural Science Foundation of China (Nos. 82022069 and 42076099), Shandong Laboratory Program (No. SYS202205), the Fundamental Research Projects of Science & Technology Innovation and Development Plan in Yantai City (No. 2023JCYJ057), Taishan Scholars Program (No. tsqn202312302), the Youth Fund from Natural Science Foundation of Shandong Province (No. ZR2023QD162), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (No. 2023-PT310-02), the Clinical Research Project of the Shanghai Municipal Health Commission (No. 20244Y0009), the Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDB1060000), and the Key R&D Program of Shandong Province (No. 2024CXPT028).

Supplementary information

Supporting information for this study can be obtained by contacting the corresponding authors via E-mail.

Declaration of competing interest

These authors have no conflict of interest to declare.

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