地胆草中倍半萜内酯SCP的结构修饰及其抑制NSCLC细胞的作用研究

非小细胞肺癌（NSCLC）严重威胁着人类的健康，发现有效的药物对肺癌治疗具有重要的意义。倍半萜内酯具有多样的活性一直是研究的热点，如小白菊内酯目前已在临床上用于癌症的治疗。本课题前期以地胆草中分离的倍半萜内酯scabertopin（SCP）为前体，进行结构改造获得的SCP衍生物能够有效地促进胞内活性氧（ROS）的产生从而选择性介导肺癌细胞死亡。目前设计并合成靶向ROS释放的前体化合物治疗恶性肿瘤是新药研发的热点之一。本项目基于促ROS抗癌策略，对倍半萜内酯SCP优势骨架进行针对性的结构改造，并获得结构类型新颖的倍半萜内酯SCP衍生物。随后运用多种药理手段进行体内、外抑制非小细胞肺癌细胞药效评价。最后设计并合成小分子生物素以及荧光探针，用于探索倍半萜内酯衍生物的分子靶标。以期能够获得1-2个靶点明确、活性显著的抗肿瘤先导化合物。

Non-small cell lung cancer (NSCLC) is a serious threat to human health. Thus, there is an urgent need for the discovery and development of effective anti-lung cancer agents to target NSCLC. Sesquiterpene lactones with biological diversity have attracted attention, such as parthenolide has entered clinical trial for cancer therapy. In the early stage of this project, using scaberoptopin (SCP) isolated from Elephantopus scaber L. as a precursor, SCP derivatives obtained by structural modification can inhibit lung cancer cell growth by ROS-mediated apoptosis via induction of reactive oxygen species (ROS). Currently, design and synthesis for targeting ROS release of candidate drug to treat malignant tumors is one of the hot spots. The structural modification of the sesquiterpene lactone skeleton based on a prooxidant strategy will be carried out and a serious novel type of sesquiterpene lactone derivatives will be obtained. Then, we investigate the anti-tumor effect of SCP derivatives on NSCLC by a variety of pharmacological methods in vitro and in vivo. Furthermore, small-molecular biotin-conjugated probe and fluorescent-conjugated probe will be designed and synthesized to illuminate molecular targets and mechanism of SCP derivatives. As a result, we hope to obtain 1 or 2 anti-tumor lead compounds with clear target and significant activity.