广藿香内生真菌Bipolaris sorokiniana的次级代谢产物及其抗肿瘤活性研究

Study on secondary metabolites of endophytic fungus Bipolaris sorokiniana from Pogostemon cablin and their antitumor activities

目的研究分离自广藿香中的内生真菌索氏平脐蠕孢（Bipolaris sorokiniana,A606）的活性次级代谢产物,并初步考察其抗肿瘤活性。方法采用正相硅胶柱层析、C18反相硅胶柱层析、Sephadex LH-20凝胶柱层析、高效液相色谱法以及薄层层析等色谱技术对菌株A606发酵液的乙酸乙酯萃取物进行分离纯化,并通过各种波谱分析进行结构鉴定;采用SRB染色法对化合物进行细胞毒活性研究。结果从发酵液的乙酸乙酯萃取物中分离鉴定出8个化合物,分别为麦角甾-4,6,8（14）,22-四烯-3-酮（1）、2-[4-（2-aminoethoxy）phenyl]ethanol（2）、邻苯二甲酸-二（2-乙基-己基）酯（3）、5-羟甲基糠醛（4）、3,5-二羟基甲苯（5）、对羟基苯乙醇（6）、5-甲基-2-呋喃甲醇（7）、3,4,6-trimethylcyclohex-3-en-1-ol（8）;化合物1对4种肿瘤细胞株SF-268、MCF-7、NCI-H460和Hep G-2的IC50值分别为20.84、15.31、13.62、25.45μmol/L。结论化合物1~4、7~8均为首次从该属真菌中分离得到,其中化合物1对4种肿瘤细胞具有显著的抑制作用。

Objective To study the active secondary metabolites of the endophytic fungus Bipolaris sorokiniana,A606 isolated from Pogostemon cablin and their antitumor activities. Methods The compounds were isolated and purified from the ethyl acetate extract of the strain A606 fermentation broth by silica gel,reverse phase silica gel,Sephadex-LH20,high performance liquid chromatography and preparative TLC.Their structures were identified by extensive analysis of their spectroscopic data. All isolated compounds were evaluated for their cytotoxic activities against human tumor cell lines by the SRB assay. Results Eight compounds were isolated and identified as Ergosta-4,6,8（ 14）,22-tetraen-3-one（ 1）,2-[4-（ 2-aminoethoxy） phenyl] ethanol（ 2）,Di-（ 2-ethylhexyl） phthalate（ 3）,5-（ hydroxymethyl） furan-2-carbaldehyde（ 4）,3,5-Dihydroxytoluene（ 5）,2-（ 4-Hydroxyphenyl） ethanol（ 6）,（ 5-methylfuran-2-yl）methanol（ 7）,3,4,6-trimethylcyclohex-3-en-1-ol（ 8）. Compound 1 showed cytotoxic activity against four tumor cell lines SF-268,MCF-7,NCI-H460 and Hep G-2 with IC50 values of 20.84,15.31,13.62 and 25.45μmol / L,respectively. Conclusion Compounds 1~ 4、7~ 8 were isolated from the genus Bipolaris for the first time. Compound 1 displayed the significant cytotoxic activity.