木脂素类化合物中组蛋白去乙酰化酶抑制剂的虚拟筛选  

Virtual Screening of Histone Deacetylase Receptor Inhibitor among Lignanoid Compounds

作　　者：邸珂 喻欢欢[1] 邹远军[1] 丁锐[1] 钟猛[1] 胥秀英[1] 郑一敏[1] 

机构地区：[1]重庆理工大学药学与生物工程学院,重庆400054

出　　处：《中国药房》2016年第4期494-497,共4页China Pharmacy

摘　　要：目的:虚拟筛选具有组蛋白去乙酰化酶(HDAC)抑制作用的木脂素类化合物。方法:以"木酯素""Lignanoid"为关键词,查询中国知网、维普、Pub Med等中外文数据库中相关文献,收集木脂素类化合物作为配体构建配体库,从蛋白质晶体数据库(PDB)中选取两个HDAC受体HDAC2(PDB code:4LXZ)和HDAC8(PDB code:1T69),运用SYBYL-X 2.0软件将配体和受体三维结构的活性位点进行对接,用总得分来反映配体与受体的亲和力大小。结果:将收集的345个木质素类化合物与4LXZ、1T69原配体一起构建了有347种配体的配体库,其中编号为275、271、110、200、056、258、181、129、037、270、187的配体与HDAC2和HDAC8受体有较好的亲和力,配体与受体的残基以氢键的方式结合。结论:木脂素类化合物具有抑制HDAC的作用;虚拟筛选方法可作为预测天然产物潜在活性的有效手段,为木脂素类化合物新的药理活性研究提供了快捷途径和理论指导。OBJECTIVE：To virtually screen lignanoid compounds with inhibitory effect of histone deacetylase（HDAC）by virtual screening method. METHODS：Using＂lignanoid＂as keyword,requiring CNKI,VIP,Pub Med and other database,lignanoid compounds were collected as ligand to establish ligand base,histone deacetylase receptor HDAC2（PDB code：4LXZ） and HDAC8（PDB code：1T69）were selected from PDB database,and then ligands and 3D active site of receptors were docked by SYBYL-X 2.0 software. The affinity of receptors to ligand was reflected by total score. RESULTS：345 lignanoid compounds,4LXZ and 1T69 primary ligand were used to establish ligand base which included 347 ligands. Ligands No.275,271,110,200,056,258,181,129,037,270,187 were demonstrated good affinity with receptors HDAC2 and HDAC8. Ligands and receptors residue were docked via hydrogen bond. CONCLUSIONS：Lignanoid compounds have inhibitory effect on HDAC;virtual screening method is effective in natural product activity prediction,which can provide quick access to and theoretical guidance for new pharmacological studies of lignanoid compounds.

关 键 词：木脂素 组蛋白去乙酰化酶 虚拟筛选 分子对接 

分 类 号：R965.1[医药卫生—药理学]