三种甾体化合物的糖基化修饰和体外抗肿瘤活性研究

发布时间：2018-08-07 12:45

【摘要】：随着人类科学技术的发展,人类的生活环境也在不断的恶化,雾霾、沙尘暴、臭氧空洞、水污染等等,人类在经历这种种恶劣的生存环境的同时,人类的机体也在发生改变,而绝大数却是恶性突变,其中最有代表性的是癌症,“癌”成为人们无法规避的问题。癌症也是肿瘤的一种,肿瘤是现今严重危害人类健康的一种疾病,化疗作为肿瘤治疗的一种主要手段,靠的是对肿瘤细胞有抑制作用的化学药物。目前运用于化疗临床治疗的抗肿瘤药物,都普遍存在疗效差、毒副作用大等问题,人们迫切需要寻找具有特异选择性、对人体正常细胞的损伤小、具有高效抗肿瘤作用的化学药物来代替现今的抗肿瘤药物。从药物的来源上来说,主要有两个:化学合成和天然产物的分离。本实验从药物的两个来源出发。1)通过化学合成的方法以三种甾体化合物:胆固醇(Cholesterol)、孕烯醇酮(Pregnenolone)、16,17-alpha环氧孕烯醇酮(Epoxypregnenolone)为甾体皂苷苷元通过三氯乙酰亚胺酯法合成了D-葡萄糖、L-阿拉伯糖、L-鼠李糖三种单糖结构修饰的6个甾体化合物的皂苷,分别为胆甾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,胆甾5-烯-3β-醇-3-O-β-D-吡喃阿拉伯糖苷,胆甾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-环氧孕甾-5,20-二烯-3β-醇-3-O-β-D-吡喃阿拉伯糖苷,选用Neuro-2a细胞(小鼠神经瘤细胞)作为供试细胞通过MTT法,对这六种化合物进行体外抗肿瘤活性筛选,测试结果显示该六种化合物对Neuro-2a细胞没有抑制活性。2)从天然产物来源出发,选用一株粘质沙雷氏菌发酵菌体粗提物,选用Neuro-2a细胞(小鼠神经瘤细胞)作为供试细胞,通过MTT法检测柱层析分离过程中的流分,进行抗肿瘤活性追踪,从而定向分离的到具有抗Neuro-2a细胞抗肿瘤活性的物质纯品。抑制活性测试显示对Neuro-2a细胞的24hIC50可以达到16μg/m L。通过结构鉴定为已知化合物灵菌红素。
[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 伪 17 伪 17 伪 -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.
【学位授予单位】：江西农业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R96

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