A novel Anti-Cancer Stem Cells compound optimized from the natural symplostatin 4 scaffold inhibits Wnt/beta-catenin signaling pathway

作者：Liu, Shuangwei; Gao, Xian; Zhang, Lisong; Qin, Shuanglin; Wei, Mingming; Liu, Ning; Zhao, Rui; Li, Benlong; Meng, Ye; Lin, Gang; Lu, Cheng; Liu, Xinhua; Xie, Maodun; Liu, Tongtong; Zhou, Honggang; Qi, Min^*; Yang, Guang^*; Yang, Cheng^*

来源：European Journal of Medicinal Chemistry, 2018, 156: 21-42.

DOI：10.1016/j.ejmech.2018.06.046

• ANTIMALARIAL ACTIVITY
• CANCER
• GALLINAMIDE
• ANALOGS

Cancer stem cells (CSCs) are responsible for carcinogenesis, cancer progression, relapse, metastasis and drug resistance. Therefore, the development of drug molecules targeting CSCs plays a vital role in medicinal researching field. However, there are extremely rare molecules that selectively ablate CSCs. The research and development of drugs targeting CSCs is limited due to a lack of anti-CSCs lead compounds. In this study, an anti-CSCs lead compound 35b was discovered, which was derived from the natural chemical scaffold of Symplostatin 4. This compound exhibited a significantly suppressive effect on tumor growth both in vitro and in vivo. Additionally, 35b could significantly reduce the number of melanoma tumor spheres and decrease the percentage of ALDH(+) melanoma cells. Further mechanism study illustrated that compound 35b could eliminate the melanoma CSCs by efficiently blocking Wnt/beta-catenin signaling pathway. Collectively, our findings would provide a novel chemical scaffold and alternative idea of molecular design for development of anti-CSCs drugs.

• 出版日期2018-8-5
• 单位天津大学; 药物化学生物学国家重点实验室; 南开大学