本文關鍵詞： 龍虎白蛇湯 虛擬篩選 癌癥 計算藥理學 分子對接　出處：《鄭州大學》2017年碩士論文　論文類型：學位論文

【摘要】：中藥經過了數千年臨床醫(yī)學的積累,其已經是中華民族燦爛文化的一部分。中藥現(xiàn)代化在中藥的發(fā)展過程中有著重要的作用,其不僅能推動我國中藥的快速發(fā)展,而且能推動整個現(xiàn)代醫(yī)藥產業(yè)的快速發(fā)展,并產生巨大的經濟效益和社會效益。在中藥現(xiàn)代化的進程中,中藥的作用原理和中藥的藥效物質基礎是中藥現(xiàn)代化的核心問題。龍虎白蛇湯記載于《抗癌中藥方選》,是一個抗癌復方,由龍葵、白英、白花蛇舌草、半支蓮、黃藥子、烏梅、無根藤等十一味中藥組成。它是前人經過無數的實踐總結出來的,在臨床研究中對食管癌有較好的治療效果,然而,目前對其藥理學的研究還較少。因此,對于龍虎白蛇湯的藥理學研究是一個重要的課題,并且從分子水平闡述其抗癌的作用機制也是現(xiàn)代藥學研究的一個熱點。本論文利用計算化學的方法對龍虎白蛇湯進行了藥理學研究,主要包括以下三個部分:第一,查閱相關文獻得到龍虎白蛇湯中的890種小分子化合物,在Cerius2軟件中計算其化學描述符,并進行主成分分析。然后對182個治療癌癥的藥物/類藥分子進行化學描述符的計算與主成分分析。通過Lipinski五規(guī)則和兩者的主成分分析研究,我們發(fā)現(xiàn)龍虎白蛇湯中所含的化學成分具有成藥的藥代動力學性質,并且可能含有治療癌癥的活性成分。第二,虛擬篩選,確定潛在活性成分。在Cerius2軟件中,對每個靶點和龍虎白蛇湯中的小分子進行對接打分。以原配體和受體的對接得分為閾值,取龍虎白蛇湯中的小分子與相關靶標對接得分高于閾值的小分子。然后,篩選出得分較高的活性小分子,利用Pajek軟件構建小分子-蛋白質網絡圖,并利用CintiBin軟件計算Degree和Betweeness值,根據這兩個參數值篩選出了16種可能潛在的活性抗癌成分,其中有10種分子已被報道具有抗炎、抗癌的生理活性。第三,精細對接。利用AutoDock軟件對篩選出的16種小分子與部分靶標進行對接,通過分析分子與靶標的對接數據確定了龍虎白蛇湯的主要活性成分和分子作用機制,減少了后續(xù)藥效物質基礎研究的盲目性,為分子作用機制實驗的研究和抗癌新藥的研發(fā)提供了指導。
[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.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R285

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1 畢輝杰;中藥方劑龍虎白蛇湯的計算藥理學研究[D];鄭州大學;2017年

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