title: Synthesis and the biological evaluation of arylnaphthalene lignans as anti-hepatitis B virus agents.
abstract: 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 EC(50) values of 0.06 and 0.14 microM, 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.
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Damodar
authors.initials: D
authors.lastname: Janmanchi
authors.forename: Ya Ping
authors.initials: YP
authors.lastname: Tseng
authors.forename: Kuei-Chen
authors.initials: KC
authors.lastname: Wang
authors.forename: Ray Ling
authors.initials: RL
authors.lastname: Huang
authors.forename: Chih Hsiu
authors.initials: CH
authors.lastname: Lin
authors.forename: Sheau Farn
authors.initials: SF
authors.lastname: Yeh
mesh_terms: D045744:Cell Line, Tumor; D006509:Hepatitis B / Q000188:drug therapy*; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000378:metabolism; D006513:Hepatitis B e Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D017705:Lignans / Q000737:chemistry* / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D013329:Structure-Activity Relationship; D014758:Viral Core Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D017705:Lignans; D014758:Viral Core Proteins; C505802:helioxanthin