山胡椒内生真菌Trichoderma sp.SHJN1和Perenniporia sp.SHJG1的抗肿瘤活性成分研究

Chemical Constituents of Endophytic Fungi Trichoderma sp.SHJN1 and Perenniporia sp.SHJG1 from Lindera Glauca and Their Anti-tumor Activities

目的从民族药山胡椒内生真菌Trichoderma sp.SHJN1和Perenniporia sp.SHJG1的代谢物中寻找活性先导化合物。方法采用正相硅胶、反相硅胶、Sephadex LH-20凝胶及制备型HPLC等对Trichoderma sp.SHJN1和Perenniporia sp.SHJG1发酵物进行分离纯化,再通过NMR、ESI-MS等鉴定化合物结构,同时采用人乳腺癌细胞(MCF-7)和人肺癌细胞(A549)对这些化合物的抗肿瘤活性进行初步评价。结果从2株内生真菌次级代谢产物中共分离鉴定了12个化合物:alantrypinone(1)、oryzalactam(2)、phomoindene A(3)、cis-gregatin B(4)、huaspenone B(5)、stigmasta-7,22-dien-3β,5α,6α-triol(6)、ergosterol(7)、1-deoxy-2-demethylviridiol(8)、viridiol(9)、trichodermamides A(10)、chromone(11)、对-羟基苯乙酸(12)。抗肿瘤活性评价结果显示,化合物3抑制MCF-7细胞增殖活性IC50为(62.9±1.02)μmol·L^(−1)[顺铂(cisplatin,DDP)IC50为(30.1±1.67)μmol·L^(−1)];化合物8和9抑制A549细胞增殖活性的IC50分别为(34.6±1.57)μmol·L^(−1)和(44.9±1.74)μmol·L^(−1)[DDP IC50为(20.6±1.42)μmol·L^(−1)]。结论化合物3,8和9具有潜在抗肿瘤活性。

OBJECTIVE To find lead compounds with potent bioactivities from endophytic fungi Trichoderma sp.SHJN1 and Perenniporia sp.SHJG1 from the traditional Chinese medicine Lindera glauca.METHODS The fermentation of Trichoderma sp.SHJN1 and Perenniporia sp.SHJG1 were isolated and purificated by repeated silica gel,ODS,Sephadex LH-20,and semi-preparation HPLC.The structures of compounds were performed by NMR and ESI-MS.The preliminary evaluation of anti-tumor activity of these compounds was performed by human breast cancer cells(MCF-7)and human lung cancer cells(A549).RESULTS A total of 12 compounds were purified from the above two endophytic fungi and identified as alantrypinone(1),oryzalactam(2),phomoindene A(3),cis-gregatin B(4),huaspenone B(5),stigmasta-7,22-dien-3β,5α,6α-triol(6)and ergosterol(7),1-deoxy-2-demethylviridiol(8),viridiol(9),trichodermamides A(10),chromone(11)and 4-hydroxyphenylacetic acid(12).The evaluation of antitumor activity showed that,compound 3 showed inhibitory activity on MCF-7 cell line with an IC50 value of(62.9±1.02)μmol·L^(−1)[cisplatin(DDP)IC50=(30.1±1.67)μmol·L^(−1)],while compound 8 and 9 showed inhibitory activities on A549 cell line with IC50 values of(34.6±1.57)μmol·L^(−1) and(44.9±1.74)μmol·L^(−1),respectively[DDP IC50=(20.6±1.42)μmol·L^(−1)].CONCLUSION Compounds 3,8 and 9 show potent anti-tumor effects.