白木香内生真菌多节孢Nodulisporium sp. A4的化学成分研究  

Chemical constituents of endophytic fungus Nodulisporium sp. A4 from Aquilaria sinensis

作　　者：李冬利[1] 吴正超[1,2] 陈玉婵[1] 陶美华[1] 章卫民[1] 

机构地区：[1]广东省微生物研究所广东省菌种保藏与应用重点实验室广东省微生物应用新技术公共实验室广东省华南应用微生物重点实验室-省部共建国家重点实验室培育基地,广东广州510070 [2]中国科学院南海海洋研究所,广东广州510301

出　　处：《中国中药杂志》2011年第23期3276-3280,共5页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(20902014);广东省自然科学基金项目(9451007002003074);广州市科技计划项目(09B34061446);广东省科学院优秀青年科技人才基金项目

摘　　要：目的:研究来源于药用植物白木香、具有抗肿瘤活性的内生真菌多节孢Nodulisporium sp.A4的化学成分。方法:采用马铃薯葡萄糖(PD)液体培养基培养、乙酸乙酯萃取得到内生真菌A4的发酵液和菌丝体粗提物,采用正相硅胶柱色谱、反相硅胶柱色谱、葡聚糖凝胶Sephadex LH-20柱色谱、制备薄层色谱和重结晶等方法对粗提物进行分离纯化,运用现代波谱技术(NMR,MS)结合文献对照鉴定化合物结构。采用MTT法测定化合物的体外抗肿瘤活性。结果:从内生真菌A4的发酵液中分离获得7个化合物,分别为5-methyl-2-vinyltetrahydrofuran-3-ol(1),6-methyl-2-(5-methyl-5-vinyltetrahydrofuran-2-yl)hept-5-en-2-ol(2),6α-hydroxycyclonerolidol(3),rel-(1S,4S,5R,7R,10R)-10-desmethyl-1-methyl-11-eudesmene(4),酪醇(5),8-甲氧基-1-萘酚(6),1,8-二甲氧基萘(7)。从内生真菌A4的菌丝体中分离获得3个化合物,分别为麦角甾醇(8),过氧化麦角甾醇(9),啤酒甾醇(10)。药理活性评价结果表明在作用浓度为100 mg.L-1时,化合物3和4对肿瘤细胞SF-268和NCI-H460的抑制率分别为89.1%,44.2%和82.3%,79.8%。结论:化合物1为新的天然产物,化合物2,3,7,10为首次从该属真菌中分离得到,化合物3和4对肿瘤细胞SF-268和NCI-H460的增殖具有一定的抑制作用。Objective： To investigate the chemical constituents of an endophytic fungus, Nodulisporium sp. A4, from the medicinal plant Aquilaria sinensis and search for antitumor natural products. Method： The fungus was cultured in liquid medium and extracted with EtOAc. The compounds were isolated by various chromatographic methods （silica gel, reverse silica gel, Sephadex-LH20, preparative TLC and so on） and recrystallization. Structural elucidation was conducted by extensive analysis of spectroscopic data as well as by comparison with literature reports. The antitumor activity of isolated compounds was tested by MTT method in vitro. Result： Seven compounds were isolated and identified from the broth culture, their structures were determined to be 5-methyl-2-vinyltetrahydrofuran-3-ol （1）, 6-methyl-2-（5-methyl-5-vinyltetrahydrofuran-2-yl）hept-5-en-2-ol （2）, 6α-hydroxycyclonerolidol （3）, rel-（1S,4S,5R,7R,10R）-10-desmethyl-1-methyl-11-eudesmene （4）, tyrosol （5）, 8-methoxynaphthalen-1-ol （6）, and 1,8-dimethoxynaphthalene （7）. Three compounds were isolated and identified from the mycelia as ergosterol （8）, ergosterol peroxide （9）, and cerevisterol （10）. The in vitro pharmalogical evaluation results displayed that compounds 3 and 4 showed 89.1%, 44.2% and 82.3%, 79.8% inhibition against tumor cell lines SF268 and NCI-H460 at 100 mg·L^-1, respectively. Conclusion： Compound 1 was a new natural product, compounds 2, 3, 7 and 10 were reported from the genus Nodulisporium sp. for the first time. Compounds 3 and 4 exhibited weak inhibitory effects on the proliferation of tumor cell lines SF268 and NCI-H460.

关 键 词：内生真菌 化学成分 白木香 多节孢 

分 类 号：R284[医药卫生—中药学]