白血病严重危害着患者健康及其家庭幸福，目前尚无治疗该病的特效药，从药用植物出发，从中寻找针对新靶标治疗白血病的新药候选分子是当前新药研发的有效途径。Fli-1基因作为Ets家族中的转录因子，在白血病及其他肿瘤发生发展中起重要调节作用，研究表明可将其作为肿瘤治疗的优秀新靶点。申请人从滇产两面针粗提物中发现了对Fli-1表达有显著影响的有效部位，该部位可能是研发新型抗白血病药物的潜在物质基础。本项目拟以滇产两面针为研究对象，以活性筛选为导向，采用现代天然产物化学研究技术，针对上述有效部位中的物质基础进行系统分离纯化和结构鉴定；并在此基础上，评价所得化合物靶向作用于Fli-1的抗白血病活性；通过化学修饰和活性再评价获取高活性化合物衍生物，并探讨其构效关系；研究高效低毒化合物对Fli-1靶基因表达的影响，并初探其对Fli-1的调控机制，为发展新型抗白血病药物候选分子提供物质基础和科学依据。

Leukemia seriously endangered the patients' health and their family happiness. Currently, there is not a specific treatment for leukemia. By starting from the medicinal plants, finding the new drug candidate for the new targets to treat leukemia is still the effective way of developing innovative drug. Fli-1 gene as the Ets family of transcription factors, plays an important regulatory role in the development of leukemia and other cancers, and the study shows that it can be used as the best new target for cancer therapy. In the early work study, effective extracts of Zanthoxylum nitidum from Yunnan province were found, which had specific effects on Fli-1 target gene and have significant impact on its expression.. So these extracts may be the potential material basis for developing novel anti-leukemia drugs. Therefore, the project combined with the preliminary studies will chose Zanthoxylum nitidum from Yunnan province as the research object, and the activity screening acts as the separation orientation. By using modern natural products chemistry technology, the substances of the effective extracts which had specific effects on Fli-1 target gene will be studied for the system isolation and structure identification. On the basis of the above, the activities of obtained compounds targeting Fli-1 gene against leukemia will be evaluated. By the chemical modification and re-evaluation of the active derivative, derivatives of the significant compound and their activities will be obtained, and the structure-activity relationship will explored. Furthermore, in order to elucidate the molecular mechanism of its anti-leukemia, the effects of compounds with the high activity and low toxicity to Fli-1 target gene expression will studied to provide material and scientific basis for the development of innovative anti-leukemia drug candidates.