Synthesis and biological evaluation of helioxanthin analogues |
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Authors: | Damodar Janmanchi Chih Hsiu Lin Jui-yu Hsieh Ya-ping Tseng Tai-an Chen Hong-jhih Jhuang Sheau Farn Yeh |
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Affiliation: | 1. Institute of Chemistry, Academia Sinica, Taipei, Taiwan, ROC;2. Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan, ROC |
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Abstract: | Helioxanthin and analogues have been demonstrated to suppress gene expression of human hepatitis B virus. In the continuous attempt to optimize antiviral activity, various structural motifs were grafted on the helioxanthin scaffold. Many such analogues were synthesized and evaluated for their anti-hepatitis B virus activity. Structure–activity relationships of these helioxanthin derivatives are also discussed. Among these new compounds, 15 exhibits the highest activity against HBV (EC50 = 0.06 μM). This compound can suppress viral surface antigen and DNA expression. Furthermore, viral RNA is also diminished while the core promoter is deactivated upon treatment by 15. A plausible working mechanism is postulated. Our results establish helioxanthin lignans as potent anti-HBV agents with unique mode of action. Since their antiviral mechanism is distinct from current nucleoside/nucleotide drugs, helioxanthin lignans constitute a potentially new class of anti-HBV agents for combination therapy. |
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