山地香茶菜的化学成分及其生物活性研究

	山地香茶菜的化学成分及其生物活性研究
	邱彩玲
导师	普诺·白玛丹增
关键词	山地香茶菜，二萜，细胞毒，促进溶酶体功能 Isodon oresbius, Diterpenoids, Cytotoxicity, Promotion of lysosomal function
摘要	山地香茶菜（Isodon oresbius）为小灌木，主要分布于我国云南西北部、四川西部、西藏东南部，生于海拔2100~3400 m的山坡或灌丛中。在四川甘孜以全草入药，内服治内脏肿块出血。为了探究不同生境下香茶菜属植物次生代谢产物的多样性，本课题对采自云南省香格里拉市虎跳峡的山地香茶菜进行了系统的化学成分及生物活性研究。通过各种色谱分离技术，现代波谱学方法以及单晶X-ray衍射等手段，从28 Kg干燥样品中共分离鉴定了62个化合物，其中二萜类化合物40个，包括新化合物12个 (isoresbins A?L)。化合物isoresbins A (1)和B (2)具有新颖的15(8→11)-迁移-6,7-裂环-7,20-内酯-对映-贝壳杉烷骨架。利用真空离心法实现了化合物1的单晶培养，通过X-ray单晶衍射分析确定了其绝对构型。对化合物1在八株人肿瘤细胞株的细胞毒活性进行了筛选，其对六株人肿瘤细胞系表现出显著的抑制作用，IC50值为2.1?4.04 μM。初步作用机制研究表明，化合物1能够诱导肿瘤细胞凋亡和细胞周期阻滞于G2/M期，破坏线粒体膜电位。同时，对10个新化合物开展了促进溶酶体功能的活性筛选，其中化合物isoresbins A (1) 和E (9) 能够促进溶酶体降解功能。本研究结果表明，该生境下的山地香茶菜中二萜化合物结构类型多样，虽然化合物1具有15(8→11) 迁移的结构特征，却仍然表现出了较好的细胞毒活性，表明α,β-不饱和酮仍为该类型化合物的重要药效团。以上研究工作不仅进一步丰富了香茶菜属植物二萜的研究内容，同时为开展基于新颖分子的结构修饰研究提供新的创造空间。; Isodon oresbius is a small shrub, which is mainly distributed on hillside or shrubs in the northwest Yunnan, western Sichuan and southeast Tibet at an altitude of 2100~3400 m. This species has long been used as medicine in Ganzi, Sichuan Province to treat visceral mass bleeding. To explore the diversity of the secondary metabolites of Isodon oresbius in different habitats, a systematic study of Isodon oresbius was conducted on its chemical composition and biological activity collected in the middle Tiger Leaping Gorge of Shangrila City. By means of chromatography methods, spectroscopic evidences, and single-crystal X-ray diffraction analysis, 62 compounds, including 40 diterpenoids (12 new ones, isoresbins A?L), have been isolated and identified from 28 kg dried materials. Isoresbins A (1) and B (2) were identified as novel 15(8→11)-abeo-6,7-seco-7,20-lactone-ent-kauranoids. Furthermore, the single crystal of compound 1 was cultured by the method of vacuum centrifugation, and was performed by the X-ray single crystal diffraction experiment to determine the absolute configuration of compound 1. The cytotoxic activity of compound 1 was tested on eight human tumor cells. It showed inhibitory effect on six human tumor cell lines with the IC50 value in the range of 2.1?4.04 μM. The preliminary mechanism study showed that compound 1 can induce tumor cell apoptosis and cell cycle arrest in G2/M phase, and destroy mitochondrial membrane potential. At the same time, the activity screening of ten new compounds to promote lysosomal function was carried out. The results showed that isoresbins A (1) and E (9) could promote lysosomal degradation function. The study disclosed the structural diversity of diterpenoids from Isodon oresbius in this habitat. Although compound 1 had the structural characteristics of 15(8→11)-abeo-, it still showed good cytotoxic activity, indicating that α,β-unsaturated ketones are still an important pharmacophore of this type of compounds. The above research not only further enriches the research content of diterpenes in Isodon, but also provides a new creative space for the research of structural modification based on novel molecules.
语种	中文
	2022-05
学位授予单位	中国科学院大学
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/75170
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	邱彩玲. 山地香茶菜的化学成分及其生物活性研究[D]. 中国科学院大学,2022.

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