生理活性天然产物是现代化学、药学和生物学等领域共同关注的科学议题，是化学生物学研究的天然素材。本项目拟选取三例化学结构复杂、生理活性（生物学表象）明确、且各具特色的天然产物或类天然产物，开展它们的化学合成、结构修饰和探针化，并结合蛋白组学研究方法，运用发展的分子工具开展相关的生物学作用靶点的垂钓研究，进而阐述相关生理活性的机制。具体研究对象为：(1) 著名的抗疟抗肿瘤天然产物青蒿素(Artemisinin, Qinghaosu, QHS); (2) 选择性抗肿瘤活性番荔枝内酯(annonaceous acetogenin)类似物AA005; 以及 (3) 具有多种生理活性的乌头生物碱Nominine。本项目研究所发展的化学合成、化学生物学研究方法和技术可望扩展到其它类型天然产物的研究之中，并对其它重要天然产物的类似研究计划具有参考借鉴价值。

Bioactive natural products and their analogues are common subjects of studies in modern chemistry and biomedical sciences, particularly chemical biology. Three of such compounds with complex molecular architectures, i.e. artemisinin (an outstanding antimalarial and anticancer terpenoid peroxide), an annonaceous acetogenin mimic AA005 (a natural polyketide-like compound with potent anticancer activity) and nominine (a highly toxic diterpenoid alkaloid in TCM), are selected as the research targets for this project; their chemical synthesis, structural modification and development of molecular probes assisted by proteomics protocols will be carried out. And the developed molecular tools will be applied to the identification of biological targets and exploration of the detailed mechanisms of action of these compounds. The methodologies and protocols of organic synthesis and chemical biology, which will be developed in this project, are expected to be generally valuable and applicable in the corresponding studies of other important bioactive natural products.