摘要
海洋复杂多变的环境造就了海洋微生物的多样性。海洋微生物因其特殊的生存环境和代谢方式,产生了许多结构独特、骨架新颖的次级代谢产物,这些化合物显示了良好的抗肿瘤、抗细菌或抗真菌等生物活性,为新药的开发和各种疑难疾病的治愈提供了新的希望。
本论文对南海沿海海藻内生真菌ZJ27次级代谢产物进行研究,通过实验室发酵培养,硅胶柱和凝胶柱反复层析、重结晶及高效液相色谱法纯化,共分离得到10个化合物,它们分别为:核丛青霉素(2-1)、ochrephilone(2-2)、6-[(3E,5E)-5,7-二甲基-2-酮基-3,5-壬二烯基]-2,4-二羟基-3-甲基苯甲醛(2-3)、(2E,4E)-4,6二甲基-2,4-辛二烯酸(2-4)、pencolide(2-5)、大黄素-9, 10-蒽二酮(2-6)、大黄素甲醚(2-7)、大黄素-1,6-二甲醚(2-8)、大黄素(2-9)、大黄酚(2-10)。其中,化合物2-1、2-2、2-3为一组结构较独特的化合物,化合物2-6、2-7、2-8、2-9、2-10为对苯醌类系列化合物。
本论文也对南海丛生盔形珊瑚内生真菌XW4-12的次级代谢产物进行研究,分离得到11个化合物,它们分别是3-[[2,3-dihydro-4,5-bis(3-methyl-2-buten-1-yl)-2- (1,1- Dimethyl-2-propen-1-yl)-1H-indol-3-yl]methyl]-2,5-piperazinedi(3-1)、3,3'-Diisopropyl -2,3,5a,6,11,11a,2',3',5'a,6',11',11'a-dodecahydro-[10b,10'b]bi [pyrazino[1',2':1,5] pyrrolo [2,3-b] indolyl]-1,4,1',4'-tetraone(3-2)、1,8-Dihydroxy-6-methoxy-9, 10-dioxo-9, 10- dihydroanthracene-3-carboxylic acid(3-3)、环(脯-甘)二肽(3-4)、环(亮-脯)二肽(3-5)、甘露醇(3-6)、尿嘧啶(3-7)、麦角甾醇(3-8)、过氧麦角甾醇(3-9)、三羟基麦角甾醇(3-10)、丁二酸(3-11)。化合物3-1结构较复杂,化合物3-2结构新颖且对称,化合物3-8、3-9、3-10为甾醇类化合物。化合物3-2核磁数据为首次公布。
同时,对部分化合物进行抑菌和酶抑制活性研究。采用96孔板法测定化合物对细菌的抑制活性,并用生长速率法测定化合物对真菌的抑制活性。结果表明:化合物2-1对枯草芽孢杆菌、白色葡萄球菌和藤黄八叠球菌有很好的抑制作用,其MIC值分别为0.1、0.2、0.2 mmol/L;化合物2-1和2-2对黑曲霉、尖孢镰刀菌、立枯丝核菌和白色念珠菌也有很好的抑制作用,2-1对这四种菌的IC50分别为15.06、3.09、3.68、8.19 mmol/L,2-2为22.28、21.32、8.18、21.75 mmol/L。化合物2-2、3-5对乙酰胆碱酯酶有抑制作用,IC50分别为0.0905、0.0985 mmol/L;化合物2-2、2-3、3-3、3-5对α-葡萄糖苷酶有抑制作用,IC50分别为0.0868、0.1049、0.1009、0.1013 mmol/L;化合物2-1、2-2、2-3、2-4、3-3对DNA拓扑异构酶I也有较好的抑制活性。
本论文系统的对海洋真菌ZJ27和XW4-12次级代谢产物及其活性进行研究,结果显示这两株海洋真菌含有丰富的化合物,而且大部分化合物都具有良好的抑菌和酶抑制活性,因此,这两株菌经优化培养可望成为药源微生物。
The complex and changeable ocean's environment has caused the marine microorganism's multiplicity. The marine microorganisms because of their special survival environment and metabolism way, have been produced much novel secondary metabolites with novel skeleton .These compounds have demonstrated antitumor,antibacterial,antifungal or other bioactivities, which have provided the new hope for the new medicine development and difficult disease cure.
The metabolites of seaweed endophytic fungi ZJ27 were studied in this master's thesis and ten compounds were isolated. The structures were identified by comprehensive physic-chemical properties and spectral methods as sclerotiorin (2-1),ochrephilone (2-2),6-((3E,5E)-5,7-dimethyl-2-methylenenona-3,5-dienyl)-2,4-dihydroxy-3-methylbenzaldehyde (2-3) ,( 2E,4E ) -4,6-dimethylocta-2,4-dienoic acid ( 2-4 ), pencolide ( 2-5 ) , 1,3,8-trihydroxy-6-methyl-9,10-anthraquinone(2-6), physcion(2-7), emodindi- methylether(2-8), emodin(2-9), chrysophanol(2-10). Among them, compounds 2-1、2-2、2-3 were structural unique and compounds 2-6、2-7、2-8、2-9、2-10 were series of benzene quinone compounds.
The metabolites of Galaxea fascicularis endophytic fungi XW4-12 were studied in this thesis and eleven compounds were isolated. The structures were 3-[[2,3-dihydro-4,5-bis (3-methyl-2-buten-1-yl) -2-(1,1-dimethyl-2-propen-1-yl)-1H-indol-3-yl]methyl]-2,5- piperazinedi(3-1)、3,3'-diisopropyl-2,3,5a,6,11,11a,2',3',5'a,6',11',11'a-dodecahydro- [10b, 10'b]bi [pyrazino[1',2':1,5] pyrrolo [2,3-b] indolyl]-1,4,1',4'-tetraone(3-2)、1,8-dihydroxy- 6-methoxy-9,10-dioxo-9,10-dihydroanthracene-3-carboxylic acid(3-3)、cyclo-(Pro-Gly)(3-4)、cyclo-( Leu - Pro)(3-5)、mannitol(3-6)、pyridin(3-7)、ergosterol(3-8)、7,22(E)-ergostadiene-3β,5α,6β-triol(3-9)、7,22-(E)–diene-3β,5α,6β-triol-ergosta(3-10)、3,5-dihydroxy ergosta-7,22-diene-6-keteon(3-11)。And compounds 3-1、3-2were structural unique and compounds 3-8、3-9、3-10were series of sterol compounds. Besides, it reported the NMR data of compound 3-2 for the first.
Meanwhile,the study was about antibacterial activity and enzyme inhibition activity of these compounds. The study determined their inhibitory activity of bacteria and fungi by the 96-well plate method and growth rate method respectively. Compound 2-1 had remarkable inhibition of Bacillus subtilis, Staphylococcus albus and Sarcina luteus, and the MIC were 0.1, 0.2, 0.2 mmol/L. Compounds 2-1 and 2-2 had notable inhibition of Aspergillus niger, Fusarium oxysporum, Rhizoctonia solani and Candida albicans, which the IC50 of compound 2-1 was 15.06、3.09、3.68、8.19 mmol/L and that of compound 2-2 was 22.28、21.32、8.18、21.75 mmol/L. Compounds 2-2, 3-5 had inhibition of cholinesterase and the IC50 were 0.0905、0.0985 mmol/L. Compounds 2-2、2-3、3-5、3-3 had inhibition ofα-glycosidase and the IC50 were 0.0868、0.1049、0.1013、0.1009mmol/L. Compounds 2-1、2-2、2-3、2-4、3-3 had inhibition of DNA topological I and the IC50 were 0.0868、0.1049、0.1013、0.1009 mmol/L.
The master's thesis was about the metabolites of marine fungi ZJ27 and XW4-12 and their activity, which results showed that marine fungi not only contained rich compounds, and most of the compounds had the good antibacterial activity and enzyme inhibition activity. Therefore, they may develop to be medical source microorganism.
引文
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