本课题在前一个国家自然科学基金面上项目结题、后续开展了活性天然成分的手性衍生物合成，发现了一个新天然来源骨架的手性紫罗兰酮生物碱衍生物ION-31a，具有很强的抗乳腺癌细胞转移作用，裸鼠移植瘤实验不仅验证了抗乳腺癌肺转移作用，而且具有抗血管生成作用。本课题以ION-31a为先导化合物，开展构效关系和结构优化研究，同时以ION-31a为活性基团合成两类探针分子研究鉴定抗肿瘤转移作用靶点；另一方面，以分子细胞药理学手段，结合靶点研究结果，阐明衍生物抗肿瘤转移作用分子机制，最后通过优选活性衍生物的体内药效评价发现成药性更高的新药候选化合物。

After finished the last project of NSFC, we continued this research to focus on the chiral derivative synthesis of bioactive natural compound, found a derivative ION-31a with new natural structure skeleton, which had significant anti-metastasis effect on human breast cacer cell, and showed anti-metastasis and anti-angiogenesis effects on implantation model of human breast carcinoma in nude mice. In this project, we study on the structure-relationship and structural optimization of lead compound ION-31a, synthesized two types of probe molecules by using the active group of ION-31a, used for identification of the target molecules. On the basis of the target research, the molecular mechanism of ION-31a is demonstrated by using molecular pharmacological method. Finally, the new drug candidates are found by in vivo evaluation on active derivatives of ION-31a.