藏药材植物内生菌来源之新颖抗癌活性化合物的靶向获取

我们拟从青藏高原产40～50种藏药材植物中尽量分离出较多内生菌，通过细胞毒活性筛选出可产生抗癌活性代谢产物的菌种，然后利用串联质谱、液-质及液-核联用分析等获得这些内生菌提取物中各化学成分的分子量、分子式及质谱裂解和氢谱等结构信息，结合文献调研选出含有较多可能为新化合物之代谢产物的约10株目标内生菌进行扩大发酵，进而对发酵产物开展靶向分离纯化，即一方面通过细胞毒筛选进行活性追踪，另一方面利用色谱、液-质联用和串联质谱进行化学信息追踪，避开大量已知化合物的分离鉴定工作，重点针对可能是新化合物的成分进行靶向分离纯化，然后对可能为新的单体化合物进行结构鉴定和进一步的体内体外抗癌活性评价，以期发现结构新颖的抗癌活性化合物和先导结构。药用植物来源的内生菌可增加活性化合物的发现率，青藏高原的环境特殊性从生源上为新颖结构的发现提供了可能，活性和化学结构信息靶向追踪为新化学成分的发现凝练目标和提高效率。

In this project, endophytes will be isolated from about 40-50 species of Tibetan medicinal plants as much as possible. Based on the cytotoxic active screening and the chemical information obtained by tandem MS, HPLC-MSn and HPLC-NMR analysis, combined with the results of literature investigation, the priority of about 10 strains which probably contain more unknown and active compounds will be chosen to targeted separate for obtaining novel compound. Namely, using cytotoxic active screening and HPLC, HPLC-MS and tandem MS analysis as probes of active and chemical information to avoid heavy work of isolation and identification of known compounds, just targeted separate and identify those novel antitumor compounds. Endophytes of medicinal plants improve the chances of discovery of active compounds; specificities of Tibetan plants provide the source of novel structures; targeted tracking of active and chemical information help us improving the efficiency in novel compound discovery. The possibility and efficiency of obtaining and discovering of new natural compounds and leading structures could be improved by targeted separation from endophytes of Tibetan medicinal plants.