Design, synthesis, and bioevaluation of paeonol derivatives as potential anti-HBV agents

Tsurng-Juhn Huang; Hong Chuang; Yu-Chuan Liang; Hui-Hsien Lin; Jia-Cherng Horng; Yu-Cheng Kuo; Chia-Wen Chen; Fu-Yuan Tsai; Shih-Chieh Yen; Shih-Ching Chou; Ming-Hua Hsu

doi:10.1016/j.ejmech.2014.11.050

Design, synthesis, and bioevaluation of paeonol derivatives as potential anti-HBV agents

Eur J Med Chem. 2015 Jan 27:90:428-35. doi: 10.1016/j.ejmech.2014.11.050. Epub 2014 Nov 26.

Authors

Affiliations

¹ School of Medicine, China Medical University, Taichung 404, Taiwan.
² Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan; Nuclear Science & Technology Development Center, National Tsing Hua University, Hsinchu 30013, Taiwan.
³ Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan.
⁴ Division of Radiotherapy, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
⁵ Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan.
⁶ Department of Radiation Oncology, China Medical University Hospital, Taichung 404, Taiwan; Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 404, Taiwan.
⁷ Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan; School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.
⁸ Center for General Education, Chang Gung University, Taoyuan 33302, Taiwan.
⁹ Development Center for Biotechnology, 101, Lane 169, Kangning St., Xizhi District, New Taipei City 22180, Taiwan.
¹⁰ Nuclear Science & Technology Development Center, National Tsing Hua University, Hsinchu 30013, Taiwan.
¹¹ Nuclear Science & Technology Development Center, National Tsing Hua University, Hsinchu 30013, Taiwan. Electronic address: mhhsu@mx.nthu.edu.tw.

PMID: 25461891
DOI: 10.1016/j.ejmech.2014.11.050

Abstract

Hepatitis B virus (HBV) is a causative reagent that frequently causes progressive liver diseases, leading to the development of acute, chronic hepatitis, cirrhosis, and eventually hepatocellular carcinoma (HCC). Despite several antiviral drugs including interferon-α and nucleotide derivatives are approved for clinical treatment for HBV, critical issues remain unresolved, e.g., low-to-moderate efficacy, adverse side effects, and resistant strains. In this study, novel Paeonol-phenylsulfonyl derivatives were synthesized and their antiviral effect against HBV was evaluated. The experimental results indicated that these compounds process significant antiviral potential, including the inhibition of viral antigen expression and secretion, and the suppression of HBV viral DNA replication. Among compounds synthesized in this research, compound 2-acetyl-5-methoxyphenyl 4-methoxybenzenesulfonate (7f) had the most potent inhibitory activity with IC50 value of 0.36 μM, and high selectivity index, SI (TC50/IC50) 47.75; which exhibited an apparent inhibition effect on viral gene expression and viral propagation in cell culture model. So, we believe our compounds could serve as reservoir for antiviral drug development.

Keywords: Anti-HBV agent; HBV; Hepatitis B virus; Paeonol; Phenylsulfonyl group.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetophenones / chemical synthesis
Acetophenones / chemistry
Acetophenones / pharmacology*
Antiviral Agents / chemical synthesis
Antiviral Agents / chemistry
Antiviral Agents / pharmacology*
Cell Survival
Dose-Response Relationship, Drug
Drug Design*
Hep G2 Cells
Hepatitis B virus / drug effects*
Humans
Microbial Sensitivity Tests
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Acetophenones
Antiviral Agents
paeonol