基于特定靶标研发新药是实施精准医疗的前提与保障，肿瘤分子靶向治疗是抗肿瘤药物研究的发展方向。以G-四链体为靶点，通过干扰原癌基因表达水平或抑制端粒酶活性，极有望成为最安全、最有效的治疗肿瘤的理想途径。本课题基于前一项基金项目所建立的基于G-四链体靶点的NMR筛选方法，从骆驼蓬子中发现具有靶向端粒和c-myc G-四链体的新颖结构的化合物，进而对骆驼蓬不同药用部位和同属其他植物进行深入研究。采用HPLC-DAD/LC-MS化学筛选和基于靶标的分子水平和细胞水平的活性筛选双重导向，快速发现靶向G-四链体的新颖结构，阐明与G-四链体结合的化合物的抗肿瘤作用机制，进一步确认靶标新颖、结构独特的抗肿瘤先导化合物；同时为从天然药物中寻找具有靶向作用的小分子化合物探索新的思路。通过构效关系的研究，为抗肿瘤靶向药物的设计提供依据，在加快抗肿瘤创新药物研究开发方面具有重要的科学意义。

The research and development of specific targets-based new drugs is precondition and guarantee of precision medicine. Molecular targeted therapy is the development direction of antitumor drugs. Interfere on the express of proto-oncogene and inhibition on the activity of telomerase might be the safe, effective ideal pathway for cancer therapy. In the previous NSFC project, the G-quadruplex-targeted NMR screen method was established and novel compounds targeting G-quadruplex of telomere and c-myc from the seeds of Peganum harmala L. were discovered. This project focuses on the further study of new alkaloids from other parts of P. harmala L. and other species of the genus Peganum. Guided by the chemical screen of HPLC-DAD/LC-MS combined with bioassay of molecule and cell levels, novel G-quadruplex-targeted compounds will be discovered. The antitumor mechanism of G-quadruplex-binding compounds will be clarified. The above research results will lay foundation for the discovery of antitumor leads with novel targets and unique structures, and explore a new path for searching small molecular compounds with targeting effects. The SAR study will provide foundation for the design of molecule-targeted antitumor drugs, and play an important role in the R&D of innovative antitumor drugs.