兩株植物病原真菌的次級代謝產(chǎn)物化學及生物活性研究
發(fā)布時間：2018-09-04 14:48
【摘要】：人類面臨著包括癌癥在內(nèi)的近2.5萬至3萬種疾病的威脅,但能治愈的疾病只占一小部分。為了加快發(fā)現(xiàn)藥物先導化合物的速度,研究者把目光轉(zhuǎn)向特殊生境真菌。特殊生境來源的真菌為適應特殊環(huán)境因素的刺激,可能產(chǎn)生新的次級代謝途徑和新的代謝產(chǎn)物,生物體為了適應特殊的環(huán)境而產(chǎn)生的化合物,往往具很好生物活性從而具有潛在的治療作用。本研究以特殊生境來源的植物病原真菌小球腔菌(Leptosphaeria sp.)和錐毛殼菌(Coniochaeta cephalothecoides)為實驗材料,在對其小樣發(fā)酵產(chǎn)物的初步活性篩選與化學指紋分析的基礎上,對其次級代謝產(chǎn)物進行了詳細的化學結(jié)構(gòu)研究和生物活性評價。對兩株菌的發(fā)酵粗提物進行分離純化,從Leptosphaeria sp.(編號GB10)中分離獲得1個新的生物堿類化合物(1),一個已知生物堿化合物(2),2個不飽和脂肪酸衍生物(3-4)和1個腦苷脂類化合物(5);從Coniochaeta cephalothecoides(編號F821)中分離獲得2個新的生物堿類化合物(6-7),3個已知生物堿類化合物(8-10),1個色氨酸衍生物(12)和2個酚酸類化合物(11,13)。共獲得了13個化合物,其中3個為新結(jié)構(gòu)化合物;并通過質(zhì)譜(Mass Spectrometry)、核磁共振譜(Nuclear Magnetic Resonance Spectroscopy)等方法確定了新化合物的平面結(jié)構(gòu)及相對構(gòu)型。對所分離化合物進行了針對不同腫瘤細胞株的細胞毒和抗炎活性評價。結(jié)果表明:化合物1、2、8、9、10對A549、K562、H460分別具有中等強度的細胞毒活性;化合物3和4在25μM濃度下表現(xiàn)了較好的抑制小鼠單核巨噬細胞中NO釋放的能力,NO合成抑制率分別為77.60%和80.94%,化合物5對抑制鼠單核巨噬細胞NO釋放的抑制活性IC50為80μM。通過對兩株植物病原菌的的化學研究,發(fā)現(xiàn)了具有不同程度的腫瘤細胞毒或抗炎活性的次級代謝產(chǎn)物。上述結(jié)果表明,植物病原菌,特別是生存環(huán)境獨特、化學研究較少的植物病原菌,是新結(jié)構(gòu)活性次級代謝產(chǎn)物的一個新的重要來源,值得進行更系統(tǒng)、深入的活性篩查與化學研究。
[Abstract]:Humans face the threat of nearly 25000 to 30, 000 diseases, including cancer, but only a small proportion of them are curable. To speed up the discovery of drug-leading compounds, the researchers turned their attention to specific habitat fungi. Fungi from special habitats may produce new secondary metabolic pathways and new metabolites to adapt to the stimulation of special environmental factors, compounds produced by organisms in order to adapt to special circumstances, Often has very good biological activity and thus has the potential therapeutic effect. In this study, (Leptosphaeria sp.) from plant pathogenic fungi from special habitats was studied. On the basis of the preliminary activity screening and chemical fingerprint analysis of the fermentative products of (Coniochaeta cephalothecoides), the chemical structure and bioactivity of its secondary metabolites were studied in detail. The fermentative crude extracts of two strains of bacteria were isolated and purified from Leptosphaeria sp.. One new alkaloid compound (1), one known alkaloid compound (2), two unsaturated fatty acid derivatives (3-4) and one brain-glycoside compound (5) were isolated from Coniochaeta cephalothecoides (No. F821. Alkaloids (6-7), three known alkaloids (8-10), one tryptophan derivative (12) and two phenolic acids (1113). A total of 13 compounds were obtained, three of which were novel compounds, and the planar structure and relative configuration of the new compounds were determined by (Mass Spectrometry), NMR (Nuclear Magnetic Resonance Spectroscopy) and other methods. The cytotoxicity and anti-inflammatory activity of the isolated compounds were evaluated for different tumor cell lines. The results showed that compound 1: 1 was of moderate cytotoxic activity to A549K562H460. Compounds 3 and 4 showed a good inhibitory effect on NO release from murine mononuclear macrophages at the concentration of 25 渭 M. The inhibitory rates of no synthesis were 77.60% and 80.94%, respectively. The inhibitory activity of compound 5 on NO release from murine mononuclear macrophages was 80 渭 M. The secondary metabolites with different degrees of cytotoxicity or anti-inflammatory activity were found by chemical studies of two plant pathogens. These results indicate that plant pathogens, especially those with unique living environment and less chemical studies, are important sources of secondary metabolites of new structures and activities, and deserve more systematic studies. In-depth activity screening and chemical research.
【學位授予單位】：河北大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R915
本文編號：2222481
[Abstract]:Humans face the threat of nearly 25000 to 30, 000 diseases, including cancer, but only a small proportion of them are curable. To speed up the discovery of drug-leading compounds, the researchers turned their attention to specific habitat fungi. Fungi from special habitats may produce new secondary metabolic pathways and new metabolites to adapt to the stimulation of special environmental factors, compounds produced by organisms in order to adapt to special circumstances, Often has very good biological activity and thus has the potential therapeutic effect. In this study, (Leptosphaeria sp.) from plant pathogenic fungi from special habitats was studied. On the basis of the preliminary activity screening and chemical fingerprint analysis of the fermentative products of (Coniochaeta cephalothecoides), the chemical structure and bioactivity of its secondary metabolites were studied in detail. The fermentative crude extracts of two strains of bacteria were isolated and purified from Leptosphaeria sp.. One new alkaloid compound (1), one known alkaloid compound (2), two unsaturated fatty acid derivatives (3-4) and one brain-glycoside compound (5) were isolated from Coniochaeta cephalothecoides (No. F821. Alkaloids (6-7), three known alkaloids (8-10), one tryptophan derivative (12) and two phenolic acids (1113). A total of 13 compounds were obtained, three of which were novel compounds, and the planar structure and relative configuration of the new compounds were determined by (Mass Spectrometry), NMR (Nuclear Magnetic Resonance Spectroscopy) and other methods. The cytotoxicity and anti-inflammatory activity of the isolated compounds were evaluated for different tumor cell lines. The results showed that compound 1: 1 was of moderate cytotoxic activity to A549K562H460. Compounds 3 and 4 showed a good inhibitory effect on NO release from murine mononuclear macrophages at the concentration of 25 渭 M. The inhibitory rates of no synthesis were 77.60% and 80.94%, respectively. The inhibitory activity of compound 5 on NO release from murine mononuclear macrophages was 80 渭 M. The secondary metabolites with different degrees of cytotoxicity or anti-inflammatory activity were found by chemical studies of two plant pathogens. These results indicate that plant pathogens, especially those with unique living environment and less chemical studies, are important sources of secondary metabolites of new structures and activities, and deserve more systematic studies. In-depth activity screening and chemical research.
【學位授予單位】：河北大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R915
【參考文獻】
相關(guān)期刊論文 前7條
1 格桑曲珍;普布多吉;林永成;劉嵐;徐愛國;陳彬;;西藏龍膽內(nèi)生真菌Leptosphaeria sp.YY-B4的次級代謝產(chǎn)物研究[J];農(nóng)業(yè)與技術(shù);2016年16期
2 郭田;夏漢祥;劉美;廖美德;;利用植物病原真菌除草的研究進展[J];世界農(nóng)藥;2012年02期
3 劉新月;李凡;陳海如;郭俊;張萍;;致病性尖孢鐮刀菌生物防治研究進展[J];云南大學學報(自然科學版);2008年S1期
4 楊祚斌;鄭家文;;山葵墨入病的綜合防治技術(shù)[J];長江蔬菜;2007年03期
5 唐永紅;曹庸;盧成瑛;黃早成;;特殊生境微生物及其活性代謝產(chǎn)物研究進展[J];微生物學通報;2006年04期
6 王輅;褚以文;;微生物來源先導化合物的研究策略[J];中國天然藥物;2006年03期
7 章元壽;;植物病原真菌毒素的研究現(xiàn)狀[J];真菌學報;1991年03期
相關(guān)博士學位論文 前1條
1 王全新;植物病原真菌活性產(chǎn)物的化學研究[D];中國科學技術(shù)大學;2013年
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