中药苦豆子具有清热解毒、祛风燥湿、止痛杀虫等功效，临床用于治疗多种癌症，疗效确切。前期研究发现苦豆子中多个喹诺里西啶类生物碱抑制拓扑异构酶Topo，抗肿瘤活性远强于阳性药物依托泊苷，极具应用前景；同时发现苦豆子还存在微量强活性成分，限于常规分离技术的灵敏度未能分离成功。为此，拟利用课题组专利纳米固定化成熟技术，以商品化TopoⅠ和TopoⅡ为靶标，制备靶蛋白杂化纳米花亲和材料，从苦豆子中靶向捕获强活性成分，并结合UPLC-QTOF-MS技术高效分离鉴定化合物，并利用细胞毒实验模型、报告基因技术确证化合物抗肿瘤活性，优选1-2个极具前景的活性化合物深入研究。建立DNA松弛、DNA断裂检测模型及整体动物荷瘤抑制模型，研究化合物的抑制活性、抑制类型及方式，明确活性化合物通过抑制TopoⅠ/II酶活性发挥抗肿瘤作用机理，有望从苦豆子中获得机制清楚、成药性好的先导化合物，为创新药物开发奠定基础。

Sophora alopecuroides L. belongs to leguminous Sophora plant，which has a variety of effects such as detoxification, expelling wind and dampness, relieving pain and insecticide. It is used to obtain better curative effect in the treatment of a variety of cancers in the clinic. It was found that several quinolone alkaloids has a strong inhibitory activity for topoisomerase Topo in Chinese medicine Sophora alopecuroides L., and their inhibitory activity is far stronger than that of the positive drug etoposide in our past work. But due to the limited sensitivity of separation technology, low content active compounds of Sophora alopecuroides failed to be separated. Therefore, the proper bio-targets TopoⅠ and Topo II would be used to prepare new affinity materials base on the target protein hybrid nano-flowers which could be used to capture the new active ingredients from Sophora alopecuroides. And these compounds would be isolated and identified combined with UPLC-QTOF-MS technology. Cytotoxic test and report gene technology would be used to confirm the antitumor activity of compounds. Then, 1-2 lead compounds are selected for further study. The inhibitory activity and inhibiting TopoⅠ / II mechanism of lead compounds would be studied by DNA relaxation, DNA fragmentation detection model, and in vivo tumor-bearing animal model. It is expected that a clear mechanism and good lead compounds are obtained from Sophora alopecuroides L.