非洲马铃果中微量MIAs的研究及tabersonine的结构修饰

	非洲马铃果中微量MIAs的研究及tabersonine的结构修饰; Investigations on the Trace MIAs from Voacanga africana and Structure Modification of Tabersonine
	赵倩
导师	张于
摘要	Monoterpene indole alkaloids (MIAs) is an important class of alkaloids with a variety of biological activities. In our previous study, we found that a series of aspidosperma-type MIAs from various plants showed significant inhibitory activity against tumor cell proliferation. Cell cycle experiments proved that this type of alkaloids induce tumor cell apoptosis by blocking the G2/M phase of the cell cycle. The competitive binding experiments and molecular docking experiments further showed that this type of alkaloids could bind on the functional domain of colchicine sites by inhibiting the tubulin polymerization, more importantly, the class of alkaloids also showed significant cell proliferation inhibitory activity against vincristine-resistant multidrug resistant cell lines (KB-VIN). Microtubules are main components of the cytoskeleton, composed of α- and β-tubulin heterodimers. Microtubules played a key role in cell morphology, intracellular transport, signal transduction, cell division and other cellular processes. Under regulation of centrosomes, microtubules polymerize to form a spindle, which lead to the separation of chromosomes into two daughter cells during mitosis. Interference with spindle microtubules could lead to the arrest of mitosis and induce cell apoptosis. Hence, microtubules have became one of the important drug targets of anti-tumor agents, and tubulin inhibitors have also became a class of effective antitumor drugs. We selected the seeds of Voacanga africana Staphf which are rich in aspidosperma-type alkaloids and 4%-6% tabersonine as our object. In this thesis, the enrichment of tabersonine and trace alkaloid components of Voacanga africana seeds were studied, the cytotoxic and acetylcholinesterase inhibitory activities of the isolates were evaluated. Meanwhile, tabersonine derivatives were prepared and the cytotoxic and tubulin inhibitory activities of the compounds, as well as their structure-activity relationships were further studied. This thesis was divided into three chapters. The first chapter is about the research on the chemical constituents and the biological activity research of the alkaloids from the seeds of V. africana. Various separation methods, modern spectroscopy technology, and computational chemistry methods have been used to isolate and identify 43 MIAs from the V. africana seeds collected from Ghana, Africa, of which 14 are new compounds, including 7 monomers and 7 dimers of aspidosperma-type MIAs. Compounds 1-3 are rare dimers substituted with acetone group at C-5', and C-14 of compound 8 is connected with an oxygenenated methylene group, which possessed an additional rare carbon unit within natural products. The isolats are mostly aspidosperma-type MIAs, followed by yohimbine, eburnean, vinblastine and other types of MIAs. Considering the folk medicinal background of Voacanga africana, 14 new compounds (1-14) were tested for cytotoxicity using the MTT method. And monomers 9 and 10 were showed signifi
	2021-05
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74529
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	赵倩. 非洲马铃果中微量MIAs的研究及tabersonine的结构修饰, Investigations on the Trace MIAs from Voacanga africana and Structure Modification of Tabersonine[D],2021.

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
赵倩-赵倩-20182801064201（8002KB）	学位论文		限制开放	CC BY-NC-SA	请求全文