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: Hong Zhang, Yanfei Qi, Yanhua Ding, Juan Wang, Qingmei Li, Jingzhou Zhang, Yanfang Jiang, Xiumei Chi, Juan Li, Junqi Niu
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 22 Issue 4 Pg. 1664-9 (Feb 15 2012) ISSN: 1464-3405 [Electronic] England
• PMID: 22264474 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antiviral Agents
• Silicon Compounds
• Tungsten Compounds
• Niobium
• tungstate

Topics

• Antiviral Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line
• Crystallography, X-Ray
• Hepatitis B virus (drug effects)
• Humans
• Niobium (chemistry)
• Silicon Compounds (chemical synthesis, chemistry, pharmacology)
• Tungsten Compounds (chemical synthesis, chemistry, pharmacology)