1. Anti-HBV Activities of Cembranoids from the South China Sea Soft Coral Sinularia pedunculata and Their Structure Activity Relationship.
- Author
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Huang C, Jin Y, Sun RN, Hu KY, Yao LG, Guo YW, Yuan ZH, and Li XW
- Subjects
- Animals, Structure-Activity Relationship, Humans, China, Hep G2 Cells, Dose-Response Relationship, Drug, Molecular Conformation, Molecular Structure, Microbial Sensitivity Tests, Crystallography, X-Ray, Anthozoa chemistry, Hepatitis B virus drug effects, Antiviral Agents pharmacology, Antiviral Agents chemistry, Antiviral Agents isolation & purification, Diterpenes pharmacology, Diterpenes chemistry, Diterpenes isolation & purification
- Abstract
Hepatitis B Virus (HBV) infection is a global public health challenge that seriously endangers human health. Soft coral, as a major source of terpenoids, contains many structurally novel and highly bioactive compounds. Sixteen cembranoids (1-16), including a new one named sinupedunol B (16), were isolated from the South China Sea Soft coral Sinularia pedunculata. The structure of the sinupedunol B (16) was determined through a combination of spectroscopic analysis and X-ray single-crystal diffraction. In this study, cembranoids isolated from Sinularia pedunculata were found of anti-HBV activity for the first time. Among them, flexilarin D (6) showed significant anti-HBV activity with an IC
50 value of 5.57 μM without cytotoxicity. We then analyzed the structure-activity relationship (SAR). Furthermore, it is demonstrated that flexilarin D (6) can accelerate the formation of capsid, inhibit HBeAg, HBV core particle DNA, HBV total RNA and pregenomic RNA in a dose dependent manner. We also confirmed the anti-HBV activity of 6 in HepG2-NTCP infection system. Finally, we demonstrated the anti-HBV mechanism of these compounds by inhibiting the ENI/Xp enhancer/promoter., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)- Published
- 2024
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