基于HPLC-DAD-MS策略的新奇笼状聚酮化合物发现及其抗肿瘤活性研究

Trichoderma sp.XY24,a mangrove endophytic fungus, was isolated from fresh leaves of the mangrove Xylocarpus granatum. Two hexaketide-derived dimeric compounds with a new cage skeleton were isolated from the extract of this fungus and their absolute configurations were determined. In this proposal, we focus on hexaketide-derived dimeric compounds from the extract of this endophytic fungus in order to find novel hexaketide-derived dimeric compounds using the HPLC-DAD-MS method and their antitumor activities. Large-scale culture and solvent extract will be employed for Trichoderma sp., and its hexaketide-derived dimeric compounds will be isolated and separated by various column chromatographies, such as silica, Sephadex LH-20 column chromatographies, and high-performance liquid chromatography. Structures of new hexaketide-derived dimeric compounds and their absolute configurations will be established by high-resolution mass spectrometry, nuclear magnetic resonance spectrocsopy, and single-crystal X-ray diffraction methods, etc. Antitumor activities of new hexaketide-derived dimeric compounds will be screened and the targeting cell signal pathways of active compounds will be clarified in order to find new types of antitumor leading compounds.

从红树木果楝新鲜叶肉组织中分离鉴定1株内生木霉菌（Trichoderma sp.XY24），并已从该菌发酵物中分离鉴定了2个新型笼状骨架聚己酮二聚体化合物。本项目拟基于HPLC-DAD-MS法分析的基础上对该木霉菌进行培养基优选优化、放大规模培养，并运用正反相硅胶柱层析、葡聚糖凝胶柱层析，以及在HPLC-DAD-MS指导下利用高效液相色谱制备等手段对笼状骨架聚己酮二聚体系列次生代谢产物进行分离，并利用现代色谱波谱技术、X-射线单晶衍射等方法确立新笼状骨架聚己酮二聚体化合物的结构及绝对立体构型。在此基础上筛选它们的抗肿瘤活性及作用靶通路，发现新结构类型的抗肿瘤活性先导化合物。

对8株红树林内生真菌中通过化学表观遗传调控等方法对代谢产物的多样性进行了研究，共发现了63种代谢产物，其中33种为新型代谢产物，其中2种为二倍半萜类新骨架化合物，1种为生物碱类新骨架化合物，结合mPTPB等活性进行了筛选，发现共有24种代谢产物具有抗结核、抑菌、抗炎等活性。项目对海洋微生物代谢产物的深入研究与开发具有重要的理论意义与应用价值。