title: Synthesis, characterization and biological activity of a niobium-substituted-heteropolytungstate on hepatitis B virus.
abstract: To synthesise and characterize the polyoxometalate Cs(2)K(4)Na[SiW(9)Nb(3)O(40)]·H(2)O 1 for its anti-hepatitis B virus (HBV) properties by using the HepG2.2.15 cell. The methylthiazol tetrazolium assay was used to evaluate the growth inhibitory effect of Compound 1 on HepG2.2.15 cell. By using ELISA and real-time PCR, respectively, the presence of extracellular hepatitis B surface antigen (HBsAg), e antigen (HBeAg), and HBV DNA were measured. The levels of intracellular HBV DNA and mRNA were determined by using Southern blot or reverse-transcription-PCR, respectively. Intracellular distribution of antigen were measured by Western blot. A 1995 μmol/L concentration of the commercially-available hepatitis B drug, adefovir dipivoxil (ADV), was required to achieve 50% cytotoxicity against cultured cells (CC(50)) by day nine; in contrast, only 1747 μmol/L of Compound 1 was required for the same result. Treatment of HepG2.2.15 cells with Compound 1 effectively suppress the secretion of HBV antigens and HBV DNA in a dose-dependent and time-dependent manner. IC(50) values were determined to be 80 μmol/L for HBsAg, 75 μmol/L for HBeAg and 3.72 μmol/L for supernatant HBV DNA at day nine post-exposure, as opposed to 266, 296, 30.09 μmol/L, respectively, for ADV. Intracellular HBV DNA, mRNA and antigen were also found to be decreased by Compound 1. The same dose of ADV yielded a significantly less robust inhibitory effect. Compound 1 can clear HBV from hepatic cells and may represent a therapeutic agent to treat HBV infection.
authors.affiliation: Department of Hepatology, First Hospital, Jilin University, Changchun, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Qi
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Ding
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Qingmei
authors.initials: Q
authors.lastname: Li
authors.forename: Jingzhou
authors.initials: J
authors.lastname: Zhang
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xiumei
authors.initials: X
authors.lastname: Chi
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Junqi
authors.initials: J
authors.lastname: Niu
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D018360:Crystallography, X-Ray; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D009556:Niobium / Q000737:chemistry*; D017655:Silicon Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017973:Tungsten Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D017655:Silicon Compounds; D017973:Tungsten Compounds; D009556:Niobium; C045951:tungstate