title: Anti-hepatitis B virus activity of α-DDB-DU, a novel nucleoside analogue, in vitro and in vivo.
abstract: α-DDB-DU, 2'-deoxy-3'-(4,4'-dimethoxy-2'-methoxycarbonyl-5,6,5',6'-bis(methylenedioxy)-1,1'-biphenyl-2-carboxyl)uridine, is a novel nucleoside analogue accomplished by linking α-DDB (α-dimenthoxy dicarboxylate biphenyl) and DU (2'-deoxyuridine) via an ester bond. In the current study, the anti-HBV activity and hepatoprotective effect of this compound were investigated both in vitro and in vivo. In the human HBV-transfected liver cell line HepG2.2.15, α-DDB-DU effectively suppressed the secretion of the HBV antigens in a dose-dependent manner, with inhibition rate of 42.31% for HBsAg and 31.52% for HBeAg at 5 μM on day 9. In addition, it could inhibit the viral DNA replication effectively at the concentration of 5 μM, with 81.18% intracellular inhibition and 88.55% extracellular inhibition, respectively, on day 9. In the duck hepatitis B virus (DHBV) infected model, DHBV DNA levels were markedly reduced after treatment with the α-DDB-DU at the dosages of 0.8 mg/kg day, 4 mg/kg day and 20 mg/kg day. The inhibition rate of α-DDB-DU at the dose of 20 mg/kg day reached 93.75% and 89.43%, in duck serum and liver, respectively, on day 10. Furthermore, the levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) in both serum and livers were notably reduced on day 10 and histopathological evaluation of the animals' livers indicated significant improvement. In conclusion, α-DDB-DU possesses significant inhibitory activity against HBV replication and ameliorates hepatic pathology significantly.
authors: Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, PR China.
authors: Li-Yun
authors: LY
authors: Zheng
authors: Li-Min
authors: LM
authors: Zang
authors: Qing-Hua
authors: QH
authors: Yang
authors: Wen-Quan
authors: WQ
authors: Yu
authors: Xian-Zhen
authors: XZ
authors: Fang
authors: Yu-Hai
authors: YH
authors: Zhang
authors: Xue-Jie
authors: XJ
authors: Zhao
authors: Na
authors: N
authors: Wan
authors: Yue-Teng
authors: YT
authors: Zhang
authors: Qing-Duan
authors: QD
authors: Wang
authors: Jun-Biao
authors: JB
authors: Chang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D052117:Benzodioxoles / Q000494:pharmacology* / Q000627:therapeutic use; D004279:DNA, Viral / Q000032:analysis; D004372:Ducks; D005260:Female; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000821:virology; D008297:Male; D020011:Protective Agents / Q000494:pharmacology*; D014529:Uridine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C586081:2'-deoxy-3'-(4,4'-dimethoxy-2'-methoxycarbonyl-5,6,5',6'-bis(methylenedioxy)-1,1'-biphenyl-2-carboxyl)uridine; D000998:Antiviral Agents; D052117:Benzodioxoles; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D020011:Protective Agents; D014529:Uridine