Liu Sheng, Wei Wanxing, Li Yubin, Liu Xu, Cao Xiaoji, Lei Kechan, Zhou Min
Department of Chemistry, Guangxi University, Nanning 530004, PR China.
Department of Chemistry, Guangxi University, Nanning 530004, PR China.
Eur J Med Chem. 2015 May 5;95:473-82. doi: 10.1016/j.ejmech.2015.03.056. Epub 2015 Mar 27.
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.
合成了一系列苯丙素衍生物，并在HepG 2.2.15细胞中评估了它们的抗乙型肝炎病毒（HBV）活性。大多数合成衍生物显示出有效的抗HBV活性。在这些化合物中，化合物4c-1表现出最强的抗HBV活性，不仅对HBsAg（IC50 = 14.18 μM，SI = 17.85）和HBeAg（IC50 = 6.20 μM，SI = 40.82）的分泌有显著抑制作用，而且对HBV DNA复制（IC50 = 23.43 μM，SI = 10.80）也有抑制作用。讨论了苯丙素衍生物的构效关系（SARs），这对于探索和开发新型抗HBV药物的苯丙素衍生物很有用。此外，使用分子对接技术对所有合成化合物在HLA-A蛋白（PDB ID：3OX8）活性位点内进行对接研究，以探索分子相互作用以及苯丙素衍生物与该蛋白活性的分子靶点。本研究确定了一类新型的强效抗HBV药物。
