四氢-β-咔啉并三嗪类化合物的设计、合成及抗肿瘤活性评价

	四氢-β-咔啉并三嗪类化合物的设计、合成及抗肿瘤活性评价; Design, synthesis and anticancer evaluation of tetrahydro-β-carboline fused triazine compounds
	王韵
导师	秦洪波
摘要	1,2,4-triazine compounds and tetrahydro-β-carboline alkaloids have a wide range of biological activities and pharmacological effects, such as antitumor, antibacterial, antiviral, antiplatelet aggregation and other activities. Based on the good antitumor activity of these two types of compounds and the research group's previous research on triazine compounds, the design concept of tetrahydro-β-carboline fused 1,2,4-triazine compounds was proposed. The main research work of this dissertation is as follows: In the aspect of design modification, by analyzing the reported structure and mode of action of the Eg5 inhibitor, the tryptophan-substituted triazine compound tentatively explored by the research group into a tetrahydro-β-carboline-triazine hybrid. The binding ability of the two with the target protein Eg5 was confirmed by molecular docking, and the antitumor activity of the target compounds was confirmed by preliminary experiments. Based on this, using the common principles of medicinal chemistry such as molecular hybridization and bioelectronics, two series of novel compounds had been designed to obtain small molecule compounds with good antitumor activity. In terms of synthesis methodology, by using nucleophilic substitution reaction, Pictet-Spengler reaction, Suzuki coupling, and alkylation methods, 60 tetrahydro-β-carboline fused 1,2,4-triazine compounds were synthesized. None of these compounds had been reported in the literature, and their structures were confirmed by 1 H NMR, 13 C NMR, 19 F NMR and ESI-MS. In terms of biological evaluation, we selected MTS assay to evaluate the vitro antitumor activity of the tetrahydro-β-carboline fused 1,2,4-triazine compounds. A549, SMMC-7721, HL-60, MCF-7 and SW480 cell lines with high expression of Eg5 were selected. The results showed that 20 compounds showed good antitumor activity against one or more tumor cell lines, and were more sensitive to human breast cancer cell lines (MCF-7) than other cell lines, among which the series II compound Y-37 (IC 50 = 5.18 μM) and Y-38 (IC 50 = 3.80 μM) were the most significant. The series I compounds Y-1, Y-3, Y-4 showed good inhibitory effects on all five cell lines. In addition, the structure-activity relationship between the synthesized compounds was initially summarized, and the compounds Y-1, Y-3 and Y-4 with excellent antitumor activity were performed by molecular docking.
	2020-05
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74189
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	王韵. 四氢-β-咔啉并三嗪类化合物的设计、合成及抗肿瘤活性评价, Design, synthesis and anticancer evaluation of tetrahydro-β-carboline fused triazine compounds[D],2020.

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