title: Design, synthesis and biological evaluation of caudatin analogs as potent hepatitis B virus inhibitors.
abstract: Thirty-nine caudatin analogs were designed and synthesized. Their anti-hepatitis B virus (HBV) activities were evaluated in vitro. Among them, twenty-three compounds showed much better anti-HBV activity than caudatin, and eleven compounds significantly inhibited the HBV DNA replication with IC50 values < 10 μM. Interestingly, three compounds (22, 28, 29) exhibited excellent activity against the secretion of HBsAg (IC50 = 63.02 μM, 52.81 μM, 56.08 μM), HBeAg (IC50 = 204.80 μM, 173.51 μM, 70.39 μM), along with HBV DNA replication (IC50 = 24.55 μM, 5.69 μM, 8.23 μM) with lower cytotoxicity. The structure-activity relationships (SARs) of these caudatin analogs were also discussed.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Yun-Bao
authors.initials: YB
authors.lastname: Ma
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Huang
authors.forename: Chang-An
authors.initials: CA
authors.lastname: Geng
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Zhang
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. chenjj@mail.kib.ac.cn.
authors.forename: Ji-Jun
authors.initials: JJ
authors.lastname: Chen
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects*; D004279:DNA, Viral / Q000096:biosynthesis*; D015195:Drug Design; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D006801:Humans; D015394:Molecular Structure; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006027:Glycosides; D006514:Hepatitis B Surface Antigens; D013256:Steroids; C570806:caudatin