Synthesis and the biological evaluation of arylnaphthalene lignans as anti-hepatitis B virus agents

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.

In a series of synthetic helioxanthin (4) derivative, compound 32 showed the most effective suppression on hepatitis B virus surface antigen (HBsAg) and e antigen (HBeAg) production in HepA2 cells with EC50 values of 0.06 and 0.14 μM, respectively.Figure optionsDownload as PowerPoint slide