肿瘤干细胞与肿瘤耐药、复发、转移等密切相关，传统的化（放）疗会清除大部分的肿瘤细胞，但却无法消灭其干细胞，进而肿瘤干细胞又可以通过分化、增殖和扩散，再度引起肿瘤的恶化。因此抗肿瘤干细胞的新药研发是治疗肿瘤的重要途径，但目前文献报导的选择性杀灭肿瘤干细胞的化合物寥寥无几。在前期研究中，从红果樫木（Dysoxylum binectariferum）中得到一系列对结直肠癌干细胞及其细胞克隆具有较强抑制活性的flavagline类化合物，并成功设计合成了多个此类衍生物，其同样显示了较强的抗结直肠癌干细胞活性。本项目拟在此基础上，进一步设计合成相关衍生物，系统开展抗结直肠癌干细胞活性筛选，研究其抗结直肠癌干细胞构效关系，阐明抑制与肿瘤干细胞相关的Wnt信号通路的作用机制，以期从中发现1-2个具有抗结直肠癌干细胞活性的候选药物分子，为开发具有自主知识产权的抗肿瘤新药提供科学依据。

Cancer stem cells (CSCs) are responsible for the drug-resistance, metastasis, and relapse of tumor. Conventional chemotherapeutics and radiation therapy will eliminate the bulk of the tumor mass, leaving behind CSCs which could initiate differentiation, proliferation, and spreading to distant organs, leading to the aggravation of tumor again. So, the development of new drugs against CSCs is an important way to treat cancer. However, seldom compounds were found currently to selectively kill CSCs. In our previous research, a series of flavagline derivatives with good inhibition of colorectal stem cells and their cell cloning were isolated from Dysoxylum binectariferum. Moreover, some flavagline derivatives have already been designed and synthesized and part of compounds showed strong anti-colorectal stem cells activities. On the basis of previous research, we plan to further design and synthesize flavagline derivatives, evaluate the inhibitory activity for colorectal stem cells, further discuss the structure-activity relationship, and investigate mechanism of inhibiting Wnt signal pathway. We hopefully find one or two drug leads targeting colorectal stem cells, which could lay a solid foundation in discovering new cancer drugs.