射干抗肝癌活性生物碱成分的虚拟筛选研究

Virtual Screening of Active Anti-Cancer Alkaloids from Belamcanda Chinensis

目的:分析射干抗肝癌的药效物质基础及作用机制。方法:首先通过TCMSP数据库及文献检索搜集射干主要活性成分;再通过GeneCards数据库预测与肝癌相关度最高的靶点;最后,以GeneCards数据库和Drug Bank数据库为基准,整合对应靶点基因蛋白中已正式认可的药物或已批准的临床实验性、研究性药物作为阳性对照物。根据以上收集的材料,使用autodockTools 1.5.6的vina模块,采用盲性对接法进行逐一对接。结果:共获得射干活性生物碱19个,检索相关度最高的靶基因蛋白分别是BRCA1、TP53、MSH2、PTEN、MLH1、EGFR和TNF,所对应的阳性对照物分别是卢卡帕利、顺铂、阿托伐他汀、厄洛替尼、阿司匹林、阿法替尼和阿司匹林。共得到133组对接数据,多数活性生物碱与TP53、MSH2、PTEN、MLH1、TNF结合度超过阳性对照组,其中异牡荆素(Isovitexin)和鸢尾醛型新三萜(Anhydrobelachinal)与各靶点基因蛋白结合度最好。结论:通过分子对接技术预测,射干的多数活性生物碱具有抗肝癌作用,极可能以异牡荆素和鸢尾醛型新三萜为核心发挥作用,因与MSH2与MLH1结合度尤为突出,故推测可能通过DNA错配修复途径影响肝癌的发展。

Objective:To analyze the material basis of Belamcanda chinensis and its action mechanism.Methods:The main active components of Belamcanda chinensis were collected through TCMSP database search and literature review.The targets of the highest correlation with liver cancer were predicted by GeneCards database.The target proteins were integrated based on GeneCards database and drug bank database,which were from drugs approved officially or approved clinical experimental and research as the positive control.According to the above collected materials,using Vina module of autodockTools 1.5.6,the blind docking method is used for docking one by one.Results:There were 19 active alkaloids obtained from Belamcanda chinensis.The most relevant target gene proteins were BRCA1,TP53,MSH2,PTEN,MLH1,EGFR and TNF,and the corresponding positive controls were Lucapalin,Cisplatin,Atorvastatin,Erlotinib,Aspirin,Afatinib and Aspirin.There were 133 docking data in total.The binding degree of most active alkaloids to TP53,MSH2,PTEN,MLH1 and TNF was higher than that of the positive control group.Isovitexin and anhydrobelachinal had the best binding degree to the target gene proteins.Conclusion:Most of the active alkaloids of Belamcanda chinensis have anti-hepatoma effects,which was predicted by molecular docking technology.Isovitexin and anhydrobelachinal were most likely to play a central role as new type of triterpenoids.Because of the prominent binding degree with MSH2 and MLH1,it is suggested that the development of hepatoma may be affected by DNA mismatch repair pathway.