title: Synthesis and biological evaluation of helioxanthin analogues.
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.
authors: Institute of Chemistry, Academia Sinica, Taipei, Taiwan, ROC.
authors: Damodar
authors: D
authors: Janmanchi
authors: Chih Hsiu
authors: CH
authors: Lin
authors: Jui-yu
authors: JY
authors: Hsieh
authors: Ya-ping
authors: YP
authors: Tseng
authors: Tai-an
authors: TA
authors: Chen
authors: Hong-jhih
authors: HJ
authors: Jhuang
authors: Sheau Farn
authors: SF
authors: Yeh
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004279:DNA, Viral / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000188:drug therapy* / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D017705:Lignans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012367:RNA, Viral / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D017705:Lignans; D012367:RNA, Viral; C505802:helioxanthin