Medicinal Chemistry Research

, Volume 21, Issue 7, pp 1179–1187

Antiviral effects of three novel derivatives of adefovir on the replication of hepatitis B virus

Authors

  • Di Wu
    • Department of Hepatologythe First Hospital, Jilin University
    • Department of China-West MedicineTumor Hospital of Jilin Province
    • Department of Hepatologythe First Hospital, Jilin University
  • Yan-Hua Ding
    • Department of Hepatologythe First Hospital, Jilin University
  • Xin-Yu Wu
    • Department of Sanitary ChemistrySchool of Public Health, Jilin University
    • Institute of DrugsAcademy of Military Medical Sciences
  • Xiang-Wei Feng
    • Department of Hepatologythe First Hospital, Jilin University
Original Research

DOI: 10.1007/s00044-011-9616-2

Cite this article as:
Wu, D., Niu, J., Ding, Y. et al. Med Chem Res (2012) 21: 1179. doi:10.1007/s00044-011-9616-2

Abstract

Nucleoside/tide analogs are now widely used for treatment of chronic hepatitis B (CHB). However, available nucleoside/tide analogs for treatment of CHB usually have limited therapeutic effect and potential adverse effects on CHB patients. We evaluated the anti-HBV effects of three novel derivatives (compounds 1, 4, and 8) of adefovir on the replication of hepatitis B virus (HBV) and determined their cytotoxicity. The effects of those compounds on the replication of human HBV in the HepG2 2.2.15 cell line and duck HBV in infected ducks were characterized by measuring the extracellular and intracellular HBV DNA using the quantitative real-time PCR and Southern blot assays. Their cytotoxicities against HepG2 cells were evaluated by MTT and measuring the contents of mitochondrial DNA using the dot blot assay. We found that all of the compounds inhibited the production of HBV in a dose-dependent manner, similar to that of adefovir dipivoxil. Furthermore, treatment with any of the compounds reduced significantly the replication of DHBV in ducks, accompanied by a significant reduction of inflammation in the livers, and the compound 1 appeared to be a fast-acting and long-lasting anti-DHBV reagent. Importantly, all of the compounds showed little cytotoxicity against HepG2 cells, even at a concentration of 1 mM. Collectively, those novel derivatives of adefovir had potent anti-HBV activity with little adverse effect and may be therapeutic candidates for potential clinical studies.

Keywords

Hepatitis B virusNucleoside/tide analogsAntiviral drugsDucks

Copyright information

© Springer Science+Business Media, LLC 2011