本文關(guān)鍵詞： 龍虎白蛇湯 虛擬篩選 癌癥 計(jì)算藥理學(xué) 分子對(duì)接　出處：《鄭州大學(xué)》2017年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：中藥經(jīng)過(guò)了數(shù)千年臨床醫(yī)學(xué)的積累,其已經(jīng)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(guò)程中有著重要的作用,其不僅能推動(dòng)我國(guó)中藥的快速發(fā)展,而且能推動(dòng)整個(gè)現(xiàn)代醫(yī)藥產(chǎn)業(yè)的快速發(fā)展,并產(chǎn)生巨大的經(jīng)濟(jì)效益和社會(huì)效益。在中藥現(xiàn)代化的進(jìn)程中,中藥的作用原理和中藥的藥效物質(zhì)基礎(chǔ)是中藥現(xiàn)代化的核心問(wèn)題。龍虎白蛇湯記載于《抗癌中藥方選》,是一個(gè)抗癌復(fù)方,由龍葵、白英、白花蛇舌草、半支蓮、黃藥子、烏梅、無(wú)根藤等十一味中藥組成。它是前人經(jīng)過(guò)無(wú)數(shù)的實(shí)踐總結(jié)出來(lái)的,在臨床研究中對(duì)食管癌有較好的治療效果,然而,目前對(duì)其藥理學(xué)的研究還較少。因此,對(duì)于龍虎白蛇湯的藥理學(xué)研究是一個(gè)重要的課題,并且從分子水平闡述其抗癌的作用機(jī)制也是現(xiàn)代藥學(xué)研究的一個(gè)熱點(diǎn)。本論文利用計(jì)算化學(xué)的方法對(duì)龍虎白蛇湯進(jìn)行了藥理學(xué)研究,主要包括以下三個(gè)部分:第一,查閱相關(guān)文獻(xiàn)得到龍虎白蛇湯中的890種小分子化合物,在Cerius2軟件中計(jì)算其化學(xué)描述符,并進(jìn)行主成分分析。然后對(duì)182個(gè)治療癌癥的藥物/類(lèi)藥分子進(jìn)行化學(xué)描述符的計(jì)算與主成分分析。通過(guò)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(xué)成分具有成藥的藥代動(dòng)力學(xué)性質(zhì),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(duì)每個(gè)靶點(diǎn)和龍虎白蛇湯中的小分子進(jìn)行對(duì)接打分。以原配體和受體的對(duì)接得分為閾值,取龍虎白蛇湯中的小分子與相關(guān)靶標(biāo)對(duì)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(gòu)建小分子-蛋白質(zhì)網(wǎng)絡(luò)圖,并利用CintiBin軟件計(jì)算Degree和Betweeness值,根據(jù)這兩個(gè)參數(shù)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(bào)道具有抗炎、抗癌的生理活性。第三,精細(xì)對(duì)接。利用AutoDock軟件對(duì)篩選出的16種小分子與部分靶標(biāo)進(jìn)行對(duì)接,通過(guò)分析分子與靶標(biāo)的對(duì)接數(shù)據(jù)確定了龍虎白蛇湯的主要活性成分和分子作用機(jī)制,減少了后續(xù)藥效物質(zhì)基礎(chǔ)研究的盲目性,為分子作用機(jī)制實(shí)驗(yàn)的研究和抗癌新藥的研發(fā)提供了指導(dǎo)。
[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(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R285

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1 畢輝杰;中藥方劑龍虎白蛇湯的計(jì)算藥理學(xué)研究[D];鄭州大學(xué);2017年

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本文編號(hào)：1472808