如何高效、精准地发现靶点明确的抗肿瘤药物是一个热点课题。在前期工作的基础上，本项目充分应用超滤质谱技术结合制备高效液相色谱（HPLC）和超低温探头核磁共振(NMR)技术，从花椒(Zanthoxylum bungeanum)、川陕花椒(Z. piasezkii)、青花椒(Z. schinifolium)的果皮水提物中定向寻找和分离鉴定新型天然SIRT1抑制剂，并评价其抗肿瘤活性，筛选出1-2个抗肿瘤先导物，为发现靶点明确的抗肿瘤新药奠定基础。本项目的总体目标是建立一套基于超滤质谱技术结合HPLC和超低温探头NMR技术的适合于植物源SIRT1抑制剂的快速识别、精准分离和准确表征的研究方法，并以此为基础从三种花椒属植物中发现新型天然SIRT1抑制剂，评价其抗肿瘤活性，探索SIRT1抑制活性与抗肿瘤活性的关联性，这对新型抗肿瘤药物的研发具有重要的意义。

It has been a hot project that how to effectively and precisely discover target-established anticancer drugs. On the basis of obtained data, here we will use ultrafiltration mass spectrometry together with HPLC and NMR with ultra-low temprature probe to targetedly discover and isolate new naturally occuring SIRT1 inhibitors from the water extracts of fruit peel of Zanthoxylum bungeanum,Z. piasezkii, and Z. schinifolium. These isolated compounds will be evaluated for their anticancer activities and 1-2 of them will be selected as anticancer lead compounds, which will be appicable for the discovery of target-established anticancer drugs. The overall goal of this project is to develop a method for the rapid recognition, precise isolation, and accurate characterization of plant-derived SIRT1 inhibitors based on ultrafiltration mass spectrometry, HPLC, and NMR with ultra-low temprature probe technologies. By using this method, we will try to find new naturally occuring SIRT1 inhibitors from three Zanthoxylum plants, and evalute their anticancer activities. On the basis of obtained data, we will find the correlation between SIRT1 inhibition and anticancer effects, which will support the development of novel anticancer drugs.