两株植物病原真菌的次级代谢产物化学及生物活性研究

发布时间：2018-09-04 14:48

【摘要】：人类面临着包括癌症在内的近2.5万至3万种疾病的威胁,但能治愈的疾病只占一小部分。为了加快发现药物先导化合物的速度,研究者把目光转向特殊生境真菌。特殊生境来源的真菌为适应特殊环境因素的刺激,可能产生新的次级代谢途径和新的代谢产物,生物体为了适应特殊的环境而产生的化合物,往往具很好生物活性从而具有潜在的治疗作用。本研究以特殊生境来源的植物病原真菌小球腔菌(Leptosphaeria sp.)和锥毛壳菌(Coniochaeta cephalothecoides)为实验材料,在对其小样发酵产物的初步活性筛选与化学指纹分析的基础上,对其次级代谢产物进行了详细的化学结构研究和生物活性评价。对两株菌的发酵粗提物进行分离纯化,从Leptosphaeria sp.(编号GB10)中分离获得1个新的生物碱类化合物(1),一个已知生物碱化合物(2),2个不饱和脂肪酸衍生物(3-4)和1个脑苷脂类化合物(5);从Coniochaeta cephalothecoides(编号F821)中分离获得2个新的生物碱类化合物(6-7),3个已知生物碱类化合物(8-10),1个色氨酸衍生物(12)和2个酚酸类化合物(11,13)。共获得了13个化合物,其中3个为新结构化合物;并通过质谱(Mass Spectrometry)、核磁共振谱(Nuclear Magnetic Resonance Spectroscopy)等方法确定了新化合物的平面结构及相对构型。对所分离化合物进行了针对不同肿瘤细胞株的细胞毒和抗炎活性评价。结果表明:化合物1、2、8、9、10对A549、K562、H460分别具有中等强度的细胞毒活性;化合物3和4在25μM浓度下表现了较好的抑制小鼠单核巨噬细胞中NO释放的能力,NO合成抑制率分别为77.60%和80.94%,化合物5对抑制鼠单核巨噬细胞NO释放的抑制活性IC50为80μM。通过对两株植物病原菌的的化学研究,发现了具有不同程度的肿瘤细胞毒或抗炎活性的次级代谢产物。上述结果表明,植物病原菌,特别是生存环境独特、化学研究较少的植物病原菌,是新结构活性次级代谢产物的一个新的重要来源,值得进行更系统、深入的活性筛查与化学研究。
[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.
【学位授予单位】：河北大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R915

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