暗绿蒿、玫黄黄肉牛肝菌和绿盖粉孢牛肝菌抗肝癌活性成分

	暗绿蒿、玫黄黄肉牛肝菌和绿盖粉孢牛肝菌抗肝癌活性成分; Study on the Antihepatoma Constituents of Artemisia atrovirens, Butyriboletus roseoflavus and Tylopilus virens
	苏丽花
导师	陈纪军
摘要	Liver cancer is a common malignant neoplasm worldwide, and a major public health concern globally, which is the seventh most common cancer. Most of liver cancer is hepatocellular carcinoma (HCC), its clinical features are concealment, rapid progress, and poor prognosis, leading to the third highest mortality rate among all cancers in the world. There were more than 840,000 new cases of liver cancer worldwide and about 780,000 deaths due to liver cancer in 2018. Among them, about half of the new cases of liver cancer occur in China, and about three-quarters of HCCs are attributed to chronic HBV and HCV infections. At present, sorafenib, regorafenib, lenvatinib, cabozantinib, nivolumab, pembrolizumab and ramucirumab are the seven major options for the treatment of patients with advanced liver cancer. However, there still are disadvantages including drug resistance and high side effects. Therefore, it is imperative to search for the new and effective preventive drugs against human hepatoma. It has been reported that many natural products display antihepatoma activities due to their unique structure and low toxicity. The purpose of our study is to search for the antihepatoma active components with novel structure and unique mechanism. Our preliminary bioassay showed that Artemisia atrovirens, Butyriboletus roseoflavus and Tylopilus virens all demonstrated potent cytotoxic activities against three human hepatoma cell lines (HepG2, SMMC-7721 and Huh7). To further reveal the active constituents of antihepatoma from them, the thesis focused on a systematically phytochemical investigation by the guidance of bioassay and LC-MS analyses. Through various chromatographic methods involving silica gel, MCI gel CHP 20P, sephadex LH-20, Rp-C18, preparative TLC, preparative HPLC and semi-preparative HPLC, as well as modern spectroscopic techniques including HRESIMS, 1D and 2D NMR, IR, UV, X-ray crystallography and calculated ECD methods, 235 compounds were isolated and identified. Among them, 89 new compounds classified four kinds of novel skeletons, and the absolute configurations of them were established based on single crystal X-ray diffraction data and quantum chemical calculations. The types of the isolates involved monoterpenoid, sesquiterpenoid, dimeric sesquiterpenoid, trimeric sesquiterpenoid, triterpenoid, steroid, fungal pigment, cerebroside and ceramide, etc.. Bioassay toward three human hepatoma cell lines suggested 40 sesquiterpenoid dimers, 28 sesquiterpenoids, 12 steroids, two triterpenoids, two cerebrosides and one ceramide showed potent cytotoxic activities, and the dimeric sesquiterpenoids possessed better activity than others. Especially, four guaianolide dimers (1-1, 1-12, 1-14 and 1-15) exhibited the most significant cytotoxicities to the three human hepatoma cells with IC50 values of 4.4, 3.8, 7.6 and 6.7 μM (HepG2), 9.6, 4.6, 6.6 and 6.0 μM (SMMC-7721), and 7.6, 4.5, 6.9 and 5.6 μM (Huh7), respectively.
	2020-08
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74173
专题	昆明植物所硕博研究生毕业学位论文
推荐引用方式 GB/T 7714	苏丽花. 暗绿蒿、玫黄黄肉牛肝菌和绿盖粉孢牛肝菌抗肝癌活性成分, Study on the Antihepatoma Constituents of Artemisia atrovirens, Butyriboletus roseoflavus and Tylopilus virens[D],2020.

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