Synthesis, characterization and biological activity of a niobium-substituted-heteropolytungstate on hepatitis B virus

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:22

Article

Zhang, Hong²  Qi, Yanfei¹  Wang, Juan¹  Zhang, Jingzhou³  Jiang, Yanfang²  Chi, Xiumei²  Li, Juan¹  Niu, Junqi² 

[1] Jilin Univ, Sch Publ Hlth, Changchun 130021, Jilin, Peoples R China

[2] Jilin Univ, Hosp 1, Dept Hepatol, Changchun 130021, Jilin, Peoples R China

[3] Tradit Chinese Med Coll Changchun, Changchun 130021, Peoples R China

关键词: Polyoxometalates;    Cs2K4Na[SiW9Nb3O40]center dot H2O;    Antiviral agent;    Hepatitis B virus;    HepG2.2.15;   

DOI  :  10.1016/j.bmcl.2011.12.115

来源: Elsevier

【 摘 要 】

To synthesise and characterize the polyoxometalate Cs2K4Na[SiW9Nb3O40]center dot H2O 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 mu mol/L concentration of the commercially-available hepatitis B drug, adefovir dipivoxil (ADV), was required to achieve 50% cytotoxicity against cultured cells (CC50) by day nine; in contrast, only 1747 mu mol/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. IC50 values were determined to be 80 mu mol/L for HBsAg, 75 mu mol/L for HBeAg and 3.72 mu mol/L for supernatant HBV DNA at day nine post-exposure, as opposed to 266, 296, 30.09 mu mol/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. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

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