title: Design, synthesis, and bioevaluation of paeonol derivatives as potential anti-HBV agents.
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.
authors.affiliation: School of Medicine, China Medical University, Taichung 404, Taiwan.
authors.forename: Tsurng-Juhn
authors.initials: TJ
authors.lastname: Huang
authors.affiliation: Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan; Nuclear Science & Technology Development Center, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Hong
authors.initials: H
authors.lastname: Chuang
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Yu-Chuan
authors.initials: YC
authors.lastname: Liang
authors.affiliation: Division of Radiotherapy, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Hui-Hsien
authors.initials: HH
authors.lastname: Lin
authors.affiliation: Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Jia-Cherng
authors.initials: JC
authors.lastname: Horng
authors.affiliation: Department of Radiation Oncology, China Medical University Hospital, Taichung 404, Taiwan; Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 404, Taiwan.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Kuo
authors.affiliation: Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan; School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Chen
authors.affiliation: Center for General Education, Chang Gung University, Taoyuan 33302, Taiwan.
authors.forename: Fu-Yuan
authors.initials: FY
authors.lastname: Tsai
authors.affiliation: Development Center for Biotechnology, 101, Lane 169, Kangning St., Xizhi District, New Taipei City 22180, Taiwan.
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Yen
authors.affiliation: Nuclear Science & Technology Development Center, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Shih-Ching
authors.initials: SC
authors.lastname: Chou
authors.affiliation: Nuclear Science & Technology Development Center, National Tsing Hua University, Hsinchu 30013, Taiwan. Electronic address: mhhsu@mx.nthu.edu.tw.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Hsu
mesh_terms: D000098:Acetophenones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000098:Acetophenones; D000998:Antiviral Agents; C013638:paeonol
keywords: Anti-HBV agent; HBV; Hepatitis B virus; Paeonol; Phenylsulfonyl group