Design, synthesis, and bioevaluation of paeonol derivatives as potential anti-HBV agents
| Autor: | Shih Chieh Yen, Shih Ching Chou, Fu Yuan Tsai, Ming Hua Hsu, Hong Chuang, Yu-Chuan Liang, Tsurng Juhn Huang, Jia-Cherng Horng, Chia Wen Chen, Yu Cheng Kuo, Hui Hsien Lin |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Hepatitis B virus
Cirrhosis Cell Survival medicine.drug_class Microbial Sensitivity Tests Pharmacology medicine.disease_cause Antiviral Agents Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Tumor Cells Cultured medicine Humans Secretion Adverse effect IC50 Dose-Response Relationship Drug business.industry Organic Chemistry Acetophenones Hep G2 Cells General Medicine medicine.disease Virology chemistry Drug Design Hepatocellular carcinoma Antiviral drug Paeonol business |
| Zdroj: | European Journal of Medicinal Chemistry. 90:428-435 |
| ISSN: | 0223-5234 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect