中药方剂龙虎白蛇汤的计算药理学研究

发布时间：2018-01-29 06:38

本文关键词： 龙虎白蛇汤虚拟筛选癌症计算药理学分子对接　出处：《郑州大学》2017年硕士论文　论文类型：学位论文

【摘要】：中药经过了数千年临床医学的积累,其已经是中华民族灿烂文化的一部分。中药现代化在中药的发展过程中有着重要的作用,其不仅能推动我国中药的快速发展,而且能推动整个现代医药产业的快速发展,并产生巨大的经济效益和社会效益。在中药现代化的进程中,中药的作用原理和中药的药效物质基础是中药现代化的核心问题。龙虎白蛇汤记载于《抗癌中药方选》,是一个抗癌复方,由龙葵、白英、白花蛇舌草、半支莲、黄药子、乌梅、无根藤等十一味中药组成。它是前人经过无数的实践总结出来的,在临床研究中对食管癌有较好的治疗效果,然而,目前对其药理学的研究还较少。因此,对于龙虎白蛇汤的药理学研究是一个重要的课题,并且从分子水平阐述其抗癌的作用机制也是现代药学研究的一个热点。本论文利用计算化学的方法对龙虎白蛇汤进行了药理学研究,主要包括以下三个部分:第一,查阅相关文献得到龙虎白蛇汤中的890种小分子化合物,在Cerius2软件中计算其化学描述符,并进行主成分分析。然后对182个治疗癌症的药物/类药分子进行化学描述符的计算与主成分分析。通过Lipinski五规则和两者的主成分分析研究,我们发现龙虎白蛇汤中所含的化学成分具有成药的药代动力学性质,并且可能含有治疗癌症的活性成分。第二,虚拟筛选,确定潜在活性成分。在Cerius2软件中,对每个靶点和龙虎白蛇汤中的小分子进行对接打分。以原配体和受体的对接得分为阈值,取龙虎白蛇汤中的小分子与相关靶标对接得分高于阈值的小分子。然后,筛选出得分较高的活性小分子,利用Pajek软件构建小分子-蛋白质网络图,并利用CintiBin软件计算Degree和Betweeness值,根据这两个参数值筛选出了16种可能潜在的活性抗癌成分,其中有10种分子已被报道具有抗炎、抗癌的生理活性。第三,精细对接。利用AutoDock软件对筛选出的16种小分子与部分靶标进行对接,通过分析分子与靶标的对接数据确定了龙虎白蛇汤的主要活性成分和分子作用机制,减少了后续药效物质基础研究的盲目性,为分子作用机制实验的研究和抗癌新药的研发提供了指导。
[Abstract]:After thousands of years of clinical medicine accumulation, Chinese medicine has become a part of the splendid culture of the Chinese nation. The modernization of traditional Chinese medicine plays an important role in the development of traditional Chinese medicine. It can not only promote the rapid development of Chinese traditional medicine, but also promote the rapid development of the whole modern medicine industry, and produce huge economic and social benefits. The action principle of Chinese medicine and the substance foundation of Chinese medicine's effect are the core problem of the modernization of traditional Chinese medicine. Longhu White Snake decoction is recorded in the Chinese Medicinal prescription for Anticancer. It is an anticancer compound compound, which is composed of Solanum lanceolata, White Angue, and White Flower Snake. Half branch lotus, Huang Yizi, Wu Mei, no root vines and other ten Chinese medicine composition. It is the predecessor after countless practices summed up, in the clinical study of esophageal cancer has a better therapeutic effect, however. At present, there are few studies on its pharmacology. Therefore, the pharmacological research of Longhu Baishen decoction is an important subject. The mechanism of its anticancer action is also a hot topic in modern pharmacology. In this paper, the pharmacology of Longhu Baishen decoction was studied by the method of computational chemistry. The main contents are as follows: first, 890 kinds of small molecular compounds were obtained from the related literature, and the chemical descriptors were calculated in Cerius2 software. Then the chemical descriptors and principal component analysis of 182 drugs / drugs for cancer were calculated and analyzed. The Lipinski five rules and their principal component analysis were used to study them. We found that the chemical constituents contained in Longhu Baishen decoction have pharmacokinetic properties and may contain active ingredients for cancer treatment. Second, virtual screening. To identify potential active components. In Cerius2 software, each target and small molecule in Longhu White Snake Soup were docked. The threshold was the docking score between the original ligand and the receptor. The small molecules in Longhu White Snake decoction with docking score higher than the threshold value were selected. Then, the active small molecules with high score were selected, and the Pajek software was used to construct the small molecular-protein network map. The values of Degree and Betweeness were calculated by CintiBin software, and 16 possible active anticancer components were selected according to the values of these two parameters. Among them, 10 molecules have been reported to have anti-inflammatory, anti-cancer physiological activities. Third, fine docking. The selected 16 small molecules were docked with some targets by AutoDock software. By analyzing the docking data of molecular and target, the main active components and molecular action mechanism of Longhu Baishen decoction were determined, which reduced the blindness of the basic research of pharmacodynamic substances. It provides guidance for the study of molecular action mechanism and the development of new anticancer drugs.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R285

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