title: Design, synthesis, and biological evaluation of new N(4)-Substituted 2'-deoxy-2'-fluoro-4'-azido cytidine derivatives as potent anti-HBV agents.
abstract: A series of new 2'-deoxy-2'-β-fluoro-4'-azido-β-d-arabinofuranosyl cytidine derivatives bearing heteroatom-containing N(4)-substituents were designed and synthesized. Antiviral screening in HepG2.2.15 cells identified three analogs (1a, 1d &1g) with good anti-HBV activity and low cytotoxicty. Of them, compound 1g exhibited significant inhibitory activity on both HBV antigens secretion (EC50, HBsAg = 9 nM, EC50, HBeAg = 0.25 μM) and viral DNA replication (intracellular, EC50 = 0.099 μM; extracellular, EC50 < 0.01 μM).
authors.affiliation: College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, PR China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Lv
authors.affiliation: College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, PR China.
authors.forename: Wu
authors.initials: W
authors.lastname: He
authors.affiliation: College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, PR China.
authors.forename: Xianhai
authors.initials: X
authors.lastname: Tian
authors.affiliation: College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, PR China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Kang
authors.affiliation: College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, PR China.
authors.forename: Yangxue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, PR China; Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, PR China.
authors.forename: Youmei
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, PR China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, PR China.
authors.forename: Qingduan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, PR China. Electronic address: wenquan_yu@zzu.edu.cn.
authors.forename: Wenquan
authors.initials: W
authors.lastname: Yu
authors.affiliation: College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou 450001, PR China. Electronic address: changjunbiao@zzu.edu.cn.
authors.forename: Junbiao
authors.initials: J
authors.lastname: Chang
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 / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: C000596970:2'-deoxy-2'-fluoro-4'-azidocytidine; D000998:Antiviral Agents; D004279:DNA, Viral; D003841:Deoxycytidine
keywords: 2′-deoxy-2′-β-fluoro-4′-azido-β-d-arabinofuranosyl cytidines; Anti-HBV activity; HBV antigens; N(4)-substituted; Viral DNA replication