【摘要】：隨著人類科學技術的發(fā)展,人類的生活環(huán)境也在不斷的惡化,霧霾、沙塵暴、臭氧空洞、水污染等等,人類在經(jīng)歷這種種惡劣的生存環(huán)境的同時,人類的機體也在發(fā)生改變,而絕大數(shù)卻是惡性突變,其中最有代表性的是癌癥,“癌”成為人們無法規(guī)避的問題。癌癥也是腫瘤的一種,腫瘤是現(xiàn)今嚴重危害人類健康的一種疾病,化療作為腫瘤治療的一種主要手段,靠的是對腫瘤細胞有抑制作用的化學藥物。目前運用于化療臨床治療的抗腫瘤藥物,都普遍存在療效差、毒副作用大等問題,人們迫切需要尋找具有特異選擇性、對人體正常細胞的損傷小、具有高效抗腫瘤作用的化學藥物來代替現(xiàn)今的抗腫瘤藥物。從藥物的來源上來說,主要有兩個:化學合成和天然產(chǎn)物的分離。本實驗從藥物的兩個來源出發(fā)。1)通過化學合成的方法以三種甾體化合物:膽固醇(Cholesterol)、孕烯醇酮(Pregnenolone)、16,17-alpha環(huán)氧孕烯醇酮(Epoxypregnenolone)為甾體皂苷苷元通過三氯乙酰亞胺酯法合成了D-葡萄糖、L-阿拉伯糖、L-鼠李糖三種單糖結構修飾的6個甾體化合物的皂苷,分別為膽甾5-烯-3β-醇-3-O-β-D-吡喃葡萄糖苷,孕甾-5,20-二烯-3β-醇-3-O-β-D-吡喃葡萄糖苷,膽甾5-烯-3β-醇-3-O-β-D-吡喃阿拉伯糖苷,膽甾5-烯-3β-醇-3-O-β-D-吡喃鼠李糖糖苷,孕甾-5,20-二烯-3β-醇-3-O-β-D-吡喃阿拉伯糖苷,16α17α-環(huán)氧孕甾-5,20-二烯-3β-醇-3-O-β-D-吡喃阿拉伯糖苷,選用Neuro-2a細胞(小鼠神經(jīng)瘤細胞)作為供試細胞通過MTT法,對這六種化合物進行體外抗腫瘤活性篩選,測試結果顯示該六種化合物對Neuro-2a細胞沒有抑制活性。2)從天然產(chǎn)物來源出發(fā),選用一株粘質(zhì)沙雷氏菌發(fā)酵菌體粗提物,選用Neuro-2a細胞(小鼠神經(jīng)瘤細胞)作為供試細胞,通過MTT法檢測柱層析分離過程中的流分,進行抗腫瘤活性追蹤,從而定向分離的到具有抗Neuro-2a細胞抗腫瘤活性的物質(zhì)純品。抑制活性測試顯示對Neuro-2a細胞的24hIC50可以達到16μg/m L。通過結構鑒定為已知化合物靈菌紅素。
[Abstract]:With the development of human science and technology, human living environment is also deteriorating, haze, sandstorm, ozone hole, water pollution and so on. But most of them are malignant mutations, the most representative of which is cancer, "cancer" has become an unavoidable problem. Cancer is also a kind of tumor. Cancer is a disease that seriously endangers human health. As a main method of tumor treatment, chemotherapy relies on chemical drugs which can inhibit tumor cells. At present, the antitumor drugs used in the clinical treatment of chemotherapy have many problems, such as poor curative effect and great side effects. People urgently need to search for specific selectivity and small damage to human normal cells. Chemical drugs that have high-efficiency anti-tumor effects to replace current anti-tumor drugs. There are two main sources of drugs: chemical synthesis and separation of natural products. In this experiment, starting from two sources of drugs, 1) D- was synthesized by chemical synthesis from three steroids: cholesterol (Cholesterol), pregnenolone, (Pregnenolone) 1, 17-alpha epoxy-pregnenone (Epoxypregnenolone), as steroidal saponins by trichloroacetimide ester method. Saponins of six steroidal compounds modified with three monosaccharides of L-arabinose L-rhamnose, They are cholesteric 5-ene--3 尾 -alcohol -3-O- 尾 -Dpyranoside, pregnant ster-5en-20-diene -3 尾 -alcohol -3-O- 尾 -Dpyran glucoside, cholesteric 5-ene--3 尾 -alcohol -3-O- 尾 -Dpyranoside, cholesteric 5-ene--3 尾 -alcohol -3-O- 尾 -Dpyranoside, cholesteric 5-ene-3-3-O- 尾 -Dpyranoside, cholesteric 5-ene-3-3-O- 尾 -Dpyranoside. In this study, Neuro-2a cells (mouse neuroma cells) were used as test cells by MTT method, and 16 偽 17 偽 17 偽 -epoxy-20 diene -3 尾 -3-O- 尾 -Dpyranoside was used as the experimental cell line of pregnen-steroidal 20-diene -3 尾 -O- 尾 -O- 尾 -Dpyranol- 尾 -3-O- 尾 -glucopyranoside (尾 -3-O- 尾 -Dpyranoside). The antitumor activity of the six compounds was screened in vitro. The results showed that the six compounds had no inhibitory activity on Neuro-2a cells. Neuro-2a cells (mouse neuroma cells) were selected as the test cells. The flow fraction in column chromatography was detected by MTT method, and the antitumor activity was traced to the purified substance with antitumor activity of Neuro-2a cells. The inhibitory activity test showed that the 24hIC50 of Neuro-2a cells could reach 16 渭 g / mL. The structure was identified as the known compound of penicillin.
【學位授予單位】：江西農(nóng)業(yè)大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R96

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