八株放线菌次级代谢产物的分离、鉴定及其活性研究

	八株放线菌次级代谢产物的分离、鉴定及其活性研究; Study on Secondary Metabolites from Eight Actinomycete Strains and Their Biological Activities
	杨凤仙
导师	黄胜雄
摘要	Natral products have made significant contributions to drug development over the past few decades. Among all known natural products producers, microorganisms represent a prolific source of structurally novel and biologically active metabolites which not only promise significant advances in fundmental science, but also continue to serve an important role in drug discovery. Therefore, there is a general recognition that microorganisms are a hotspot in the field of natural products research. This dissertation mainly focuses on the bioactive secondary metabolites derived from actinomycetes. 662 actinomycete strains were isolated from 29 soil samples and 7 plant samples (simply remove duplicate strains based on morphological differences). Eight soil-derived strains (Streptomyces sps. KIB-H1471, KIB-H1113, KIB-H483, KIB-H1318, KIB-HW85, KIB-HW82, KIB-HA104 and KIB-H46) were selected for further chemical and biological study based on the HPLC-UV/vis diode array analysis of all the extracts obtained from the fermentation broth of the 662 strains. The significance of this study is to discover new agents with good biological activity from actinomycetes, and provide a material basis for the drug development and drug leads discovery. The selected strains were cultured by liquid fermentation technology to obtain crude extracts. Then, the crude extracts were isolated and purified by various chromatographic technologies (normal-phase silica gel column chromatography, thin-layer chromatography, Sephadex LH-20 column chromatograph, reversed-phase C18 column chromatography, etc.), and finally 77 compounds were obtained. Structure elucidation of these 77 isolates was performed by means of various techniques, including nuclear magnetic resonance spectroscopy (NMR), mass spectrum (MS), infrared spectroscopy (IR), ultraviolet spectrum (UV), circular dichroism (CD), X-ray single crystal diffraction, chemical derivatization and the comparision of spectroscopic data reported in the literatures, and 39 of them are elucidated as new compounds. Among all the new compounds, 1–7, 56, 57, 67 and 68 are benzene derivatives; 11 and 73 are pyridine alkaloids; 13–19 are piperidocyclopentane derivatives; 30–37 are phenazine analogs; 38–40 are pyranocyclopentane derivatives; 47–49 are phenoxazine analogs; 52 and 53 are γ-pyrone derivatives; 61 and 62 are anthraquinone dimers, and 69 is β-carboline analog. In this paper, the antibacterial, antitumor, anti-diabetic and immunosuppressive activities of some isolates were screened. Compounds 2, 6 and 34 showed inhibitory effect against human T cell proliferation with IC50 values of 14.3, 12.5 and 23.5 μM, respectively. Compounds 3 and 6 could weakly enhance insulin-stimulated glucose uptake. Compounds 48, 52, 53, 61 and 62 exhibited selective cytotoxicity against Hela, HL-60, A-549, SMMC-7721, MCF-7 and SW480 cell lines with IC50 values ranging between 4.0 and 38.3 μM. Compounds 56 and 62 showed antibacterial activity against Escherichia
	2020-05
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74202
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	杨凤仙. 八株放线菌次级代谢产物的分离、鉴定及其活性研究, Study on Secondary Metabolites from Eight Actinomycete Strains and Their Biological Activities[D],2020.

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