Synthesis, structure-activity relationships and biological evaluation of caudatin derivatives as novel anti-hepatitis B virus agents

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• 作者：Li-Jun Wang^a ; ^b ; Chang-An Geng^a ; Yun-Bao Ma^a ; Xiao-Yan Huang^a ; Jie Luo^a ; Hao Chen^a ; ^b ; Rui-Hua Guo^a ; ^b ; Xue-Mei Zhang^a ; Ji-Jun Chen^a ; ^{chenjj@mail.kib.ac.cn}
• 关键词：Synthesis ; Caudatin derivatives ; Anti-HBV activity ; Structure&ndash ; activity relationships
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：1 May, 2012
• 卷：20
• 期：9
• 页码：2877-2888
• 文件大小：2590 K

摘要

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 IC₅₀ values in the range of 2.82-7.48 渭M. Interestingly, two compounds (2e, 2f) had potent activity inhibiting not only the secretion of HBsAg (IC₅₀ = 18.68 渭M, 21.71 渭M), HBeAg (IC₅₀ = 13.16 渭M, 33.73 渭M), but also HBV DNA replication (IC₅₀ = 7.48 渭M, 3.63 渭M). 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.