title: Inhibition of the replication of hepatitis B virus in vitro by a novel 2,6-diaminopurine analog, beta-LPA.
abstract: Antiviral therapy of chronic hepatitis B remains a major clinical problem worldwide. Like lamivudine, nucleoside analogs have become the focus of investigation of anti-hepatitis B virus (anti-HBV) drugs. Here, beta-LPA is a novel 2,6-diaminopurine analog found to possess potent anti-HBV activity. In HepG2.2.15 cell line, beta-LPA had a 50% effective concentration (EC(50)) of 0.01 microM against HBV, as determined by analysis of secreted and intracellular episomal HBV DNA. Levels of HBV surface antigen (HBsAg) and e antigen (HBeAg) in drug-treated cultures revealed that beta-LPA had no significant inhibitory effects on HBsAg and HBeAg. beta-LPA didn't show any cytotoxicity up to 0.4 microM with a 50% cytotoxic concentration (CC(50)) of 50 microM. Furthermore, treatment with beta-LPA resulted in no apparent inhibitory effects on mitochondrial DNA content. Considering the potent inhibition of HBV DNA synthesis and no obvious toxicity of beta-LPA, this compound should be further explored for development as an anti-HBV drug.
authors.affiliation: Institute of Liver Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Xing-Xing
authors.initials: XX
authors.lastname: He
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.forename: Ju-Sheng
authors.initials: JS
authors.lastname: Lin
authors.forename: Ying
authors.initials: Y
authors.lastname: Chang
authors.forename: Bai-Xin
authors.initials: BX
authors.lastname: Ye
mesh_terms: D015075:2-Aminopurine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000998:Antiviral Agents / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000821:virology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006515:Hepatitis B virus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
chemical_list: D000998:Antiviral Agents; D015075:2-Aminopurine; C007300:2,6-diaminopurine