2. Academic Validation
  3. Synthesis and structure-activity relationship studies of parthenolide derivatives as potential anti-triple negative breast cancer agents

Synthesis and structure-activity relationship studies of parthenolide derivatives as potential anti-triple negative breast cancer agents

  • Eur J Med Chem. 2019 Mar 15;166:445-469. doi: 10.1016/j.ejmech.2019.01.058.
Weizhi Ge 1,  Xin Hao 1,  Fangzhi Han 1,  Zhongquan Liu 1,  Tianpeng Wang 1,  Mengmeng Wang 2,  Ning Chen 2,  Yahui Ding 3,  Yue Chen 4,  Quan Zhang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China.
  • 2 Accendatech Company, Ltd, Tianjin, 300384, People's Republic of China.
  • 3 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China. Electronic address: 017095@nankai.edu.cn.
  • 4 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China. Electronic address: yuechen@nankai.edu.cn.
  • 5 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China. Electronic address: zhangquan@nankai.edu.cn.
PMID: 30739826 DOI: 10.1016/j.ejmech.2019.01.058
Abstract

Triple-negative breast Cancer (TNBC) is the most aggressive cancers with a high recurrence rate and rapidly acquired drug resistance among various breast Cancer subtypes. There is no specific drug for treatment of TNBC. Discovery of therapeutic agents with unique modes of actions is urgently needed. In this study, a series of seventy parthenolide derivatives was designed, synthesized, and evaluated for their anti-TNBC activities. Compound 7d exhibited the most potent activity against different breast Cancer cells with IC50 values ranging from 0.20 μM to 0.27 μM, which demonstrated 11.6- to 18.6-fold improvement comparing to that of the parent compound parthenolide with IC50 values of 2.68-4.63 μM. It is worth to note that 7d was more active than the positive control drug ADR. Moreover, compound 7d could induce Apoptosis of SUM-159 cells through mitochondria pathway and cause G1 phase arrest of SUM-159 cells. These findings indicate that compound 7d deserves further studies as a lead compound for ultimate discovery of effective anti-TNBC drug.

Keywords

Apoptosis; Cell cycle; Parthenolide; Structure-activity relationship; Triple negative breast cancer.

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