State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China.
Bioorg Med Chem. 2012 May 1;20(9):2877-88. doi: 10.1016/j.bmc.2012.03.023. Epub 2012 Mar 16.
A series of caudatin derivatives were synthesized, and their anti-hepatitis B virus (HBV) activity was evaluated in HepG 2.2.15 cells. Most of the 3-O-substituted caudatin derivatives showed effective anti-HBV activity. Among the tested compounds, six compounds (2e-2h, 2l, 2r) exhibited significantly inhibitory activity against HBV DNA replication with IC(50) values in the range of 2.82-7.48 μM. Interestingly, two compounds (2e, 2f) had potent activity inhibiting not only the secretion of HBsAg (IC(50)=18.68 μM, 21.71 μM), HBeAg (IC(50)=13.16 μM, 33.73 μM), but also HBV DNA replication (IC(50)=7.48 μM, 3.63 μM). The structure-activity relationships (SARs) of caudatin derivatives had been discussed, which were useful for caudatin derivatives to be explored and developed as novel anti-HBV agents.
合成了一系列的娃儿藤定衍生物，并在 HepG2.2.15 细胞中评估了它们的抗乙型肝炎病毒 (HBV) 活性。大多数 3-O-取代的娃儿藤定衍生物表现出有效的抗 HBV 活性。在所测试的化合物中，有 6 个化合物（2e-2h、2l、2r）对 HBV DNA 复制具有显著的抑制活性，IC50 值在 2.82-7.48 μM 范围内。有趣的是，有两个化合物（2e、2f）不仅具有很强的抑制 HBsAg（IC50=18.68 μM、21.71 μM）和 HBeAg（IC50=13.16 μM、33.73 μM）分泌的活性，而且对 HBV DNA 复制也有很强的抑制活性（IC50=7.48 μM、3.63 μM）。讨论了娃儿藤定衍生物的构效关系（SARs），这对于探索和开发新型抗 HBV 药物的娃儿藤定衍生物具有重要意义。
