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Synthesis and the Biological Evaluation of Arylnaphthalene Lignans as Anti‐hepatitis B Virus Agents
Author(s) -
Yeh Sheau Farn,
Lin Chih Hsiu,
Janmanchi Damodar,
Tseng Ya Ping
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.526.9
Subject(s) - hepatitis b virus , virus , virology , antigen , lamivudine , hbeag , chemistry , biology , hbsag , immunology
We have previously shown that helioxanthin can suppress human hepatitis B virus gene expression. A series of helioxanthin analogues were synthesized and evaluated for their anti‐hepatitis B virus activity. Modifications at the lactone rings and methylenedioxy unit of helioxanthin can modulate the antiviral activity. Among them, compound 32 is the most effective anti‐HBV agent. Compound 32 can suppress the secretion of viral surface antigen and e antigen in HepA2 cells with EC50 values of 0.06 and 0.14 μM, respectively. Compound 32 not only inhibited HBV DNA with wild‐type and lamivudine‐resistant strain but also suppressed HBV mRNA, core protein and viral promoters. In this study, a full account of the preparation, structure‐activity relationships of helioxanthin analogues, and the possible mechanism of anti‐HBV activity of this class of compounds are presented. This type of compounds possesses unique mode of action differing from existing therapeutic drugs. They are potentially new anti‐HBV agents.