巴戟天内生真菌Diaporthe lithocarpus的次级代谢产物及其细胞毒活性研究  

Study on the Secondary Metabolites from Endophytic Fungus Diaporthe lithocarpus A740 in Morinda offcinalis and the Cytotoxic Activities

作　　者：刘慧波 陈玉婵[2] 李赛妮 刘昭明 刘洪新[2] 章卫民[2] 李冬利 LIU Hui-bo;CHEN Yu-chan;LI Sai-ni;LIU Zhao-ming;LIU Hong-xin;ZHANG Wei-min;LI Dong-li(College of Biotechnology and Health Sciences,Wuyi University,Jiangmen 529020,China;Guangdong Institute of Microbiology/State Key Laboratory of Applied Microbiology Southern China/Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application/Guangdong Open Laboratory of Microbiology Application New Technology,Guangzhou 510070,China)

机构地区：[1]五邑大学生物科技与大健康学院,广东江门529020 [2]广东省微生物研究所/华南应用微生物国家重点实验室/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,广东广州510070

出　　处：《中药材》2020年第10期2439-2444,共6页Journal of Chinese Medicinal Materials

基　　金：国家自然科学基金项目(31600271);广东省科技计划项目(2107A020211023);广州市珠江科技新星项目(201806010080)。

摘　　要：目的:研究巴戟天内生真菌Diaporthe lithocarpus A740的次级代谢产物及其细胞毒活性。方法:采用正、反相硅胶柱、凝胶柱和高效液相等多种色谱技术对菌株A740的固体发酵产物进行分离纯化,并通过NMR、MS等波谱方法鉴定化合物结构,采用SRB法对得到的单体化合物进行细胞毒活性测试。结果:从菌株A740的发酵产物中分离纯化得到13个化合物,分别鉴定为:2⁃羟基苯乙酸乙酯(1)、4⁃(2⁃羟乙基)苯甲酸(2)、4⁃羟基苯乙酸乙酯(3)、4⁃甲基⁃5,6⁃二氢吡啶⁃2⁃酮(4)、(3R,4R)⁃cis⁃4⁃hydroxy⁃5⁃methylmellein(5)、viridianol 1(6)、5⁃羟基⁃7⁃甲氧基⁃4,6⁃二甲基⁃1⁃(3H)异苯并呋喃酮(7)、phomopene(8)、diaporisoindole B(9)、diaporisoindole A(10)、p⁃苯三醇(11)、异戊二烯基异苯并呋喃A(12)、lithocarin A(13)。结论:其中,化合物1~7为首次从Diaporthe属真菌中分离得到。化合物10、12和13对神经癌细胞(SF⁃268)、人乳腺癌细胞(MCF⁃7)、人肝癌细胞(HepG2)和人肺癌细胞株(A549)四株肿瘤细胞株具有细胞毒活性,其中化合物10对这四种肿瘤细胞株的IC50为23.96~35.19μmol/L。Objective:To study the secondary metabolites from the endophytic fungus Diaporthe lithocarpus A740 derived in Morinda officinalis and their cytotoxic activities.Methods:The compounds from the solid fermentation products of an endophytic fungus Diaporthe lithocarpus A740 were isolated and purified by positive and reverse phase silica gel column chromatography,Sephadex LH⁃20 column chromatography and HPLC.The structures of compounds were identified by NMR,MS and other spectroscopic data.The isolated compounds were assayed for their cytotoxic activity by the SRB method.Results:Thirteen compounds were isolated and purified from the fermentation products of the strain A740 and identified as 2⁃hydroxyphenethyl acetate(1),4⁃(2⁃hydroxyethyl)benzoic acid(2),2⁃phenyl⁃2⁃hydroxyethyl acetate(3),4⁃methyl⁃5,6⁃dihydropyren⁃2⁃one(4),(3R,4R)⁃cis⁃4⁃hydroxy⁃5⁃methylmellein(5),viridianol 1(6),5⁃hydroxy⁃7⁃methoxy⁃4,6⁃dimethyl⁃1(3H)isobenzofuranone(7),phomopene(8),diaporisoindole B(9),diaporisoindole A(10),p⁃menthanetriol(11),isoprenylisobenzofuran A(12),lithocarin A(13),respectively.Conclusion:Among them,compounds 1 to 7 are isolated from the Diaporthe genus for the first time.Compounds 10,12,13 show inhibitory activities against four tumor cell lines,namely,neural cancer cell lines(SF⁃268),human breast cancer cell lines(MCF⁃7),human liver cancer cell lines(HepG_(2))and human lung cancer cell lines(A549),with the IC_(50) values of compound 10 ranging from 23.96 to 35.19μmol/L.

关 键 词：巴戟天 内生真菌 Diaporthe lithocarpus 次级代谢产物 细胞毒活性 

分 类 号：R284.1[医药卫生—中药学] R284.2[医药卫生—中医学]