Synthesis and Discovery Novel Anti-Cancer Stem Cells Compounds Derived from the Natural Triterpenoic Acids

  • J Med Chem. 2018 Dec 13;61(23):10814-10833. doi: 10.1021/acs.jmedchem.8b01445.
Xinhua Liu  1 ,  Benlong Li  1 ,  Zhen Zhang  1 ,  Yujiao Wei  1 ,  Zhongxin Xu  1 ,  Shuanglin Qin  1  2 ,  Ning Liu  1 ,  Rui Zhao  1 ,  Junya Peng  1 ,  Guang Yang  1 ,  Min Qi  1  3 ,  Tongtong Liu  1 ,  Maodun Xie  1 ,  Shuangwei Liu  1 ,  Xian Gao  1 ,  Cheng Lu  1 ,  Lijun Zhu  1 ,  Xinyu Long  1 ,  Hong Kang  3 ,  Tao Sun  1 ,  Honggang Zhou  1 ,  Mingming Wei  1 ,  Guang Yang  1 ,  Cheng Yang  1
Affiliations
  • 1. The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy , Nankai University , Tianjin 300071 , People's Republic of China.
  • 2. School of Pharmaceutical Science and Technology , Tianjin University , Tianjin 300072 , People's Republic of China.
  • 3. Tianjin Key Laboratory of Molecular Drug Research , Tianjin International Joint Academy of Biomedicine , Tianjin 300457 , People's Republic of China.
PMID: 30433783 DOI: 10.1021/acs.jmedchem.8b01445
Abstract

Cancer Stem Cells (CSCs) have been reported to be involved in tumorigenesis, tumor recurrence, Cancer invasion, metastasis, and drug-resistance. Therefore, the development of drug molecules targeting CSCs has become an attractive therapeutic approach. However, the molecules which can selectively ablate CSCs are extremely rare. To explore the leading compounds targeting CSCs, 52 analogues of triterpenoic acids were synthesized in this study, whose biological activities were evaluated. On the basis of the results of tumorsphere assay, two compounds 48 and 51, derived from oleanolic acid, exhibited suppressive effect on elimination of different type of CSCs. Meanwhile, compounds 48 and 51 could significantly inhibit the growth of several tumors both in vitro and in vivo. Furthermore, treatment of Cancer cells with both of two compounds would dramatically increase the level of ROS, which might eliminate the CSCs. Collectively, the leading compounds 48 and 51 were promising anti-CSCs agents that merited further validation as a novel class of chemotherapeutics.

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