title: Synthesis, structure-activity relationships and biological evaluation of caudatin derivatives as novel anti-hepatitis B virus agents.
abstract: A series of caudatin derivatives were synthesized, and their anti-hepatitis B virus (HBV) activity was evaluated in HepG 2.2.15 cells. Most of the 3-O-substituted caudatin derivatives showed effective anti-HBV activity. Among the tested compounds, six compounds (2e-2h, 2l, 2r) exhibited significantly inhibitory activity against HBV DNA replication with IC(50) values in the range of 2.82-7.48 μM. Interestingly, two compounds (2e, 2f) had potent activity inhibiting not only the secretion of HBsAg (IC(50)=18.68 μM, 21.71 μM), HBeAg (IC(50)=13.16 μM, 33.73 μM), but also HBV DNA replication (IC(50)=7.48 μM, 3.63 μM). The structure-activity relationships (SARs) of caudatin derivatives had been discussed, which were useful for caudatin derivatives to be explored and developed as novel anti-HBV agents.
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Wang
authors.forename: Chang-An
authors.initials: CA
authors.lastname: Geng
authors.forename: Yun-Bao
authors.initials: YB
authors.lastname: Ma
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Huang
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Rui-Hua
authors.initials: RH
authors.lastname: Guo
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Ji-Jun
authors.initials: JJ
authors.lastname: Chen
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006513:Hepatitis B e Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D006027:Glycosides; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D013256:Steroids; C570806:caudatin