1. Academic Validation
  2. Synthesis and biological evaluation of celastrol derivatives as anti-ovarian cancer stem cell agents

Synthesis and biological evaluation of celastrol derivatives as anti-ovarian cancer stem cell agents

  • Eur J Med Chem. 2019 Oct 1:179:667-679. doi: 10.1016/j.ejmech.2019.06.086.
Xiaojing Li 1 Jie Ding 2 Ning Li 3 Wenxia Liu 3 Fuhao Ding 3 Huijuan Zheng 3 Yanyan Ning 3 Hongmin Wang 3 Renmin Liu 4 Shaoda Ren 5
Affiliations

Affiliations

  • 1 School of Pharmacy, Liaocheng University, Shandong, 252000, People's Republic of China. Electronic address: lixiaojing@lcu.edu.cn.
  • 2 Central Laboratory, Liaocheng People's Hospital, Liaocheng, Shandong, 252000, People's Republic of China.
  • 3 School of Pharmacy, Liaocheng University, Shandong, 252000, People's Republic of China.
  • 4 School of Pharmacy, Liaocheng University, Shandong, 252000, People's Republic of China. Electronic address: liurenmin@lcu.edu.cn.
  • 5 Central Laboratory, Liaocheng People's Hospital, Liaocheng, Shandong, 252000, People's Republic of China. Electronic address: zslrsd@163.com.
Abstract

Ovarian Cancer is associated with a high percentage of recurrence of tumors and resistance to chemotherapy. Cancer Stem Cells (CSCs) are responsible for Cancer progression, tumor recurrence, metastasis, and chemoresistance. Thus, developing CSC-targeting therapy is an urgent need in Cancer research and clinical application. In an attempt to achieve potent and selective anti-CSC agents, a series of celastrol derivatives with cinnamamide chains were synthesized and evaluated for their anti-ovarian Cancer activities. Most of the compounds exhibited stronger antiproliferative activity than celastrol, and celastrol derivative 7g with a 3,4,5-trimethoxycinnamamide side chain was found to be the most potent antiproliferative agent against ovarian Cancer cells with an IC50 value of 0.6 μM. Additionally, compound 7g significantly inhibited the colony formation ability and reduced the number of tumor spheres. Furthermore, compound 7g decreased the percentage of CD44+, CD133+ and ALDH+ cells. Thus, compound 7g is a promising anti-CSC agent and could serve as a candidate for the development of new anti-ovarian Cancer drugs.

Keywords

Antiproliferative; Cancer stem cell; Celastrol derivatives; Ovarian cancer.

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