青风藤有效化学成分与环氧合酶的对接研究  

Study on Molecular Docking of Constituents of Sinomenium Acutum with Cyclooxygenase

作　　者：郑裕义[1] 汪德成[1] 冯洪涛[1] 

机构地区：[1]上海大学环境与化学工程学院,上海200072

出　　处：《化学研究》2010年第4期43-47,共5页Chemical Research

摘　　要：将青风藤中23个有效化学成分与COX-2酶对接,有四个化合物具有较低的结合自由能,其中以青藤碱为最低.进一步将这四个化合物与COX-1酶对接,发现这四个化合物与COX-1酶结合能力较弱,预示这四个化合物具有选择性抑制COX-2酶的能力.对青藤碱和COX-2以及COX-1酶的结合模式进行分析,发现青藤碱主要结合于COX-2酶的S′口袋,而COX-1酶的S′结合口袋中第523号残基由COX-2酶中的Val523变成了体积较大的Ile523,使得COX-1酶的S′结合口袋相对COX-2酶的结合口袋要小,从而导致青藤碱分子不能进入COX-1酶S′结合口袋.这成功解释了青藤碱选择性抑制COX-2酶的原因,与早期有关文献报道的实验结果相吻合,充分表明了对接模型的合理性,青藤碱等化合物可作为设计COX-2酶选择性抑制剂的先导化合物.23 active chemical components in sinomenium acutum were docked with COX-2 and COX-1, respectively. The binding mode and docking energy of those components with COX-2 and COX-1 were analyzed. It has been found that four compounds among the 23 components possess relatively lower docking energy with COX 2, and sinornenine has the lowest docking energy with COX 2. However, the four compounds have weak binding capability with COX-I, which shows that they may selectively inhibit COX-2. Analysis of binding mode indicates that sinomenine enters and binds with the S＇ active pocket of COX-2. Different from the 523rd resi due Va1523 in COX 2, Ile523, that in the S＇ pocket of COX-1, has a larger volume. Therefore, S＇ pocket of COX-1 is smaller than that of COX-2, making it harder for sinomenine molecule to enter the S＇ pocket of COX-1. This is just why sinomenine can selectively inhibit COX-2. Furthermore, sinomenine can be used as a precursor compound in designing selective inhibitor for COX-2.

关 键 词：青风藤 青藤碱 环氧合酶 COX-1 COX-2 对接 

分 类 号：O641.3[理学—物理化学]