多花蒿抗肝癌活性成分研究

	多花蒿抗肝癌活性成分研究; Anti-hepatoma cytotoxic constituents from Artemisia myriantha
	唐爽
导师	陈纪军
摘要	Hepatocellular carcinoma (HCC), characterized by an insidious onset, a rapid development, a high degree of malignancy, poor prognosis, and caused by many factors, was the fourth cause of cancer mortality worldwide with about 840,000 new cases diagnosed and more than 780,000 death cases annually. The food and drug administration (FDA) approved sorafenib as the only therapeutic agent with proved ef?cacy for the treatment of advanced HCC since 2007. Subsequently, six new drugs, including three synthetic agents (regorafenib, lenvatinib, cabozantinib) and three monoclonal antibody medicants (nivolumab, pembrolizumab, ramucirumab) have been approved by FDA since 2017. Although signi?cantly therapeutic progresses have been achieved, there are still disadvantages including the low response rate, serious side effects and drug resistance. Thus, new drugs with high efficiency and low toxicity are further needed for the treatment of HCC. Artemisia myriantha Wall. ex Bess. is a folk medicine with the effects of ''Qingre'', "Qushu'',"Liangxue'' and “Zhixue” in the Traditional Chinese Medicine system. Random screening suggested the EtOH extract of A. myriantha (Asteraceae) and its EtOAc fraction had cytotoxicity against human hepatoma cells (HepG2) with inhibitory ratios of 30.6% and 53.5% at 50.0 μg/mL. The EtOAc fraction was further separated into six subfractions (Frs. A~F) by silica gel column chromatography, of which Fr. B, Fr. C, and Fr. D possessed obvious activity with the inhibitory ratios of 68.2, 88.5, and 72.0% at 50.0 μg/mL. In order to clarify the cytotoxic constituents, bioassay-guided isolation of the most active fractions (Fr. C and Fr. D) afforded 52 compounds, including 26 new compounds, and 26 known ones were isolated from A. myriantha for the first time. Structural identification of the new compounds was carried out by detailed spectroscopic analyses (HRMS, IR, 1D and 2D NMR), and their absolute configurations were confirmed by the single-crystal X-ray diffraction or ECD calculations. The isolated compounds were classified as 39 sesquiterpenoids involving 15 germacranes (1~15), 10 guaianes (16~25), 8 eudesmanes (26~33) and 6 other types (34~39), 3 monoterpenoids (40~42), 5 lignans (43~47), 2 coumarins (48, 49), a benzofuran (50) and 2 sterols (51, 52). 26 new compounds were assigned as artemyrienolides A~S and artemyrianins A~G. The isolates were pre-assayed for their cytotoxicity on HepG2 cells at 40.0 and 20.0 μM by MTT, and 20 sesquiterpenoids demonstrated inhibitory ratios more than 50% at 40.0 μM, which were further tested for their dose-effect against three human hepatoma cell lines (HepG2, Huh7 and SMMC-7721). The results suggested that the 20 sesquiterpenoids showed cytotoxicity with IC50 values ranging from 3.1 to 185.0 μM. Importantly, artemyrienolide I (10) manifested significant cytotoxic activity on both HepG2 and Huh7 cells with IC50 values of 8.6 and 8.8 μM, and artemyrienolide H (9) demonstrated remarkable cytotoxicity to t
	2020-08
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74183
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	唐爽. 多花蒿抗肝癌活性成分研究, Anti-hepatoma cytotoxic constituents from Artemisia myriantha[D],2020.

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