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Design, Synthesis, and Bioevaluation of Matrine Derivatives as Potential Anti–Hepatitis B Virus Agents
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Design, Synthesis, and Bioevaluation of Matrine Derivatives as Potential Anti–Hepatitis B Virus Agents
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Journal Article
Design, Synthesis, and Bioevaluation of Matrine Derivatives as Potential Anti–Hepatitis B Virus Agents
2025
Overview
Hepatitis B virus (HBV) is a causative reagent that frequently causes progressive liver diseases, leading to the development of acute hepatitis, chronic hepatitis, cirrhosis, and eventually hepatocellular carcinoma. Despite several antiviral drugs, including interferon-α and nucleotide derivatives, being approved for clinical treatment of HBV, critical issues remain unresolved, e.g., their low-to-moderate efficacy and adverse side effects, as well as resistant strains. In this study, twenty-three matrine derivatives were synthesized, and their antiviral effects against HBV were evaluated. Of these, eleven compounds inhibited HBeAg secretion significantly more than the positive control, lamivudine (3TC). Among the compounds synthesized in this study, compounds 4a and 4d had the most potent inhibitory activity, with IC50 value of 41.78 and 33.68 μM, respectively. Compounds 1h, 4a, and 4d were also subjected to molecular docking studies. These compounds inhibited viral gene expression and viral propagation in a cell culture model. Thus, we believe our compounds could serve as resource for antiviral drug development.
Publisher
MDPI AG,MDPI
Subject
/ Antiviral Agents - pharmacokinetics
/ Biological response modifiers
/ diversity-oriented synthesis
/ DNA-Binding Proteins - chemistry
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - metabolism
/ Enzymes
/ Hepatitis B virus - drug effects
/ Hepatitis B virus - genetics
/ Humans
/ matrine
/ Matrines - chemical synthesis
/ Molecular Docking Simulation
/ Solvents
