娑罗子中抗炎活性成分的计算机虚拟筛选

Computer Virtual Screening of Anti-inflammatory Active Components in Semen Aesculi

利用计算机辅助药物设计探究了植物娑罗子中抗炎的活性成分。在TCMSP数据库中利用里宾斯基五规则筛选出娑罗子的化学成分,用SYBYL软件对小分子与抗炎作用相关的16个蛋白靶点进行分子对接,通过对接打分函数(Total Score≥7)筛选出活性成分;采用Discovery Studio软件分析了蛋白复合体的相互作用;利用admetSAR软件分析了对接结果较好的几个化合物的ADMET预测。结果表明:七叶皂苷苷元A与JINK3结合最好,山奈酚与iNOS结合最好,槲皮素和七叶苷与JAK1结合最好,秦皮苷ERK1、JNK3、MIF结合都好;蛋白复合体的分析结果显示疏水作用力和氢键在对接中发挥重要作用。5个化合物的ADMET存在一定的不足,成药时应该稍加修饰使其具有更好的ADMET。此研究为中药娑罗子化学成分的抗炎研究提供了参考,也为新药研发提供了理论基础。

Objective:To explore the anti—inflammatory active ingredients in plant Semen Aesculiby computer—aided drug design,the chemical constituents of Semen Aesculi were screened in the TCMSP database using the five rules of Lipinski.16tumor targets related to anti-inflammatory effects were downloaded from the PDB database,and small molecules and target proteins were molecularly docked using SYBYL software.The active ingredients were screened by the docking scoring function(Total Score ≥ 7);the interaction of protein complexes was analyzed using Discovery Studio software;the ADMET predictions of several compounds with better docking results were analyzed using admetSAR software.Results:Five chemical components with anti—inflammatory activity were screened out:aescigenin has the best combination with C—jun N—terminal kinase 3;kaempferol has the best combination with inducible nitric oxide synthase(iNOS);quercetin has the best combination with Janus kinase 1(JAK1);esculin has the best combination with Janus kinase 1(JAK1);fraxin has the best combination with Extracellular signal regulated kinase 1(ERK1);C—jun N—terminal Kinase 3 and Macrophage migration inhibitory factor(MIF)bind well;Hydrogen bond and the hydrophobic interactions played an important role in docking.There are some problems with the ADMET of 5 compounds,and they should be slightly modified to make them have better ADMET when making medicine.This study provides a reference for the anti—inflammatory study of the chemical constituents of Chinese medicine Semen Aesculi,and the explanation of the anti—inflammatory mechanism also provides a theoretical basis and reference for the development of new drugs.