Design, synthesis, biological evaluation and molecular docking studies of phenylpropanoid derivatives as potent anti-hepatitis B virus agents

  • Eur J Med Chem. 2015 May 5:95:473-82. doi: 10.1016/j.ejmech.2015.03.056.
Sheng Liu  1 Wanxing Wei  2 Yubin Li  3 Xu Liu  1 Xiaoji Cao  4 Kechan Lei  1 Min Zhou  1
Affiliations
  • 1. Department of Chemistry, Guangxi University, Nanning 530004, PR China.
  • 2. Department of Chemistry, Guangxi University, Nanning 530004, PR China. Electronic address: [email protected].
  • 3. School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, PR China.
  • 4. Center of Analysis and Testing, Zhejiang University of Industry, Hangzhou 310014, PR China.
Abstract

A series of phenylpropanoid derivatives were synthesized, and their anti-hepatitis B virus (HBV) activity was evaluated in HepG 2.2.15 cells. Most of the synthesized derivatives showed effective anti-HBV activity. Of these compounds, compound 4c-1 showed the most potent anti-HBV activity, demonstrating potent inhibitory effect not only on the secretion of HBsAg (IC50 = 14.18 μM, SI = 17.85) and HBeAg (IC50 = 6.20 μM, SI = 40.82) secretion but also HBV DNA replication (IC50 = 23.43 μM, SI = 10.80). The structure-activity relationships (SARs) of phenylpropanoid derivatives had been discussed, which were useful for phenylpropanoid derivatives to be explored and developed as novel anti-HBV agents. Moreover, the docking study of all synthesized compounds inside the HLA-A protein (PDB ID: 3OX8) active site were carried out to explore the molecular interactions and a molecular target for activity of phenylpropanoid derivatives with the protein using a moe-docking technique. This study identified a new class of potent anti-HBV agents.

Keywords
Anti-HBV activity; Molecular docking; Phenylpropanoid derivatives; Structure–activity relationships; Synthesis.