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

摘要

To synthesise and characterize the polyoxometalate Cs 2K 4Na[SiW 9Nb 3O 40] H 2O 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 lmol/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 lmol/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 lmol/L for HBsAg, 75 lmol/L for HBeAg and 3.72 lmol/L for supernatant HBV DNA at day nine post-exposure, as opposed to 266, 296, 30.09 lmol/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.