Briarane-type diterpenoids from a gorgonian coral Ellisella sp . with anti-HBV activities
Briarane-type diterpenoids from a gorgonian coral Ellisella sp . with anti-HBV activities
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来自柳珊瑚 Ellisella sp 的 Briarane 型二萜类化合物。
DOI：
10.1016/j.bioorg.2020.104423
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发表时间：
2020-12-01
影响因子：
5.1
通讯作者：
Lin, Wenhan
中科院分区：
文献类型：
--
作者：
Wu, Jiru;Li, Xiaodan;Lin, Wenhan
柳珊瑚 Ellisella sp 的化学研究。结果分离出 12 种 briarane 型二萜类化合物，其中包括 8 种新的同系物，即 ellisellolides A-H (1-8)。它们的结构通过广泛的光谱分析确定，帮助计算的 ECD 数据支持构型分配。所有化合物均在 HepAD38 细胞系中评估了体外抗 HBV 活性，而构效关系的初步分析表明 junceellolide C 具有 3E,5(16)-二烯，并且 C-6 处的氯取代是最活跃的同系物。 Junceellolide C 以剂量依赖性方式有效减少 HBV DNA、HBV RNA 和 HBeAg 的产生。它还显着减少了HBV cccDNA的补充并促进了存在的HBV cccDNA的降解。这些发现表明 junceellolide C 是 cccDNA 的转录抑制剂，并有望成为开发新型抗 HBV 药物的先导药物。
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.