通过对接、筛选和体外研究发现肟醚类化合物为乙型肝炎病毒（HBV）抑制剂。

Discovery of Oxime Ethers as Hepatitis B Virus (HBV) Inhibitors by Docking, Screening and In Vitro Investigation.

机构信息

College of Chemistry and Chemical Engineering, Guangxi University, Nanning 53004, China.

Guangxi Colleges and Universities Key Laboratory of Applied Chemistry Technology and Resource Development, Guangxi University, Nanning 53004, China.

出版信息

Molecules. 2018 Mar 12;23(3):637. doi: 10.3390/molecules23030637.

A series of oxime ethers with C₆-C₄ fragment was designed and virtually bioactively screened by docking with a target, then provided by a Friedel-Crafts reaction, esterification (or amidation), and oximation from -substituted phenyl derivatives (Methylbenzene, Methoxybenzene, Chlorobenzene). Anti-hepatitis B virus (HBV) activities of all synthesized compounds were evaluated with HepG2.2.15 cells in vitro. Results showed that most of compounds exhibited low cytotoxicity on HepG2.2.15 cells and significant inhibition on the secretion of HBsAg and HBeAg. Among them, compound showed the most potent activity on inhibiting HBsAg secretion (IC = 39.93 μM, SI = 28.51). Results of the bioactive screening showed that stronger the compounds bound to target human leukocyte antigen A protein in docking, the more active they were in anti-HBV activities in vitro.

设计了一系列具有 C₆-C₄ 片段的肟醚类化合物，通过与靶点对接进行虚拟生物活性筛选，然后通过 Friedel-Crafts 反应、酯化（或酰胺化）和肟化从取代的苯基衍生物（甲苯、苯甲醚、氯苯）得到。所有合成化合物的抗乙型肝炎病毒（HBV）活性均采用 HepG2.2.15 细胞在体外进行评估。结果表明，大多数化合物对 HepG2.2.15 细胞的细胞毒性较低，对 HBsAg 和 HBeAg 的分泌有显著抑制作用。其中，化合物表现出最强的抑制 HBsAg 分泌的活性（IC=39.93μM，SI=28.51）。生物活性筛选结果表明，对接中与靶点人白细胞抗原 A 蛋白结合越强的化合物，在体外抗 HBV 活性方面越活跃。