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Design, synthesis and biological evaluation of seco-A-pentacyclic triterpenoids-3,4-lactone as potent non-nucleoside HBV inhibitors.

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机构: [a]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China [b]Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, PR China [c]Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou 510515, PR China
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关键词: seco-A-triterpenoid-3 4-lactone HBeAg secretion inhibition HBV cccDNA replication

摘要:
A series of seco-A-pentacyclic triterpenoids-3,4-lactone were synthesized and the anti-HBV activities were evaluated in vitro. Several compounds inhibited the secretion of HBV antigen and the replication of HBV DNA in micromolar level. Compounds D7 and D10, seco-A-oleanane-3,4-lactone, suppressed the HBeAg secretion with IC50 values of 0.14 μM and 0.86 μM respectively, and the inhibitory activities were also confirmed by detecting the fluorescence intensity of FITC-labeled monoclonal mouse HBeAg antibody via flow cytometry. Compounds D7 and D10 as well as B4, ring-A cleaved 3,30-dioic acid, also displayed remarkable inhibition on both HBV DNA replication at the concentration of 25 μM and HBV cccDNA (covalently closed circularDNA) replication with IC50 values of 33.5 μM, 32.7 μM and 12.3 μM respectively. Copyright © 2018 Elsevier Ltd. All rights reserved.

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出版当年[2017]版:
大类 | 3 区 医学
小类 | 3 区 有机化学 4 区 药物化学
最新[2025]版:
大类 | 4 区 医学
小类 | 2 区 有机化学 4 区 药物化学
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第一作者机构: [a]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China
通讯作者:
通讯机构: [a]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China [c]Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou 510515, PR China [*1]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China.
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