2. Academic Validation
  3. Synthesis and evaluation of novel thiosemicarbazone and semicarbazone analogs with both anti-proliferative and anti-metastatic activities against triple negative breast cancer

Synthesis and evaluation of novel thiosemicarbazone and semicarbazone analogs with both anti-proliferative and anti-metastatic activities against triple negative breast cancer

  • Bioorg Med Chem. 2021 May 1:37:116107. doi: 10.1016/j.bmc.2021.116107.
Chengfeng Bai 1,  Shuangjie Wu 1,  Shengnan Ren 1,  Meiqi Zhu 1,  Guoshun Luo 1,  Hua Xiang 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
  • 2 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China. Electronic address: xianghua@cpu.edu.cn.
PMID: 33735799 DOI: 10.1016/j.bmc.2021.116107
Abstract

Triple-negative breast Cancer (TNBC) is one of the most aggressive Cancer with high mortality and recurrence rates. Hecogenin, a steroidal sapogenin, is reported as a potential anti-tumor agent against breast Cancer. However, the moderate activity limits its further application in clinical. With the aim to identify novel analogues that are especially efficacious in therapy of TNBC, a series of novel hecogenin thiosemicarbazone and semicarbazone derivatives were designed, synthesized and biologically evaluated. Screening of cytotoxicity revealed that 4c could potently inhibit the proliferation of breast Cancer cells (MCF-7 and MDA-MB-231 cells), lung Cancer cells (A549) and colon Cancer cells (HT-29) at low μM level. Importantly, further mechanism studies indicated the ability of 4c in inducing Apoptosis of MDA-MB-231 cells by arresting the cell cycle. Moreover, 4c notably suppressed the migration and invasion of MDA-MB-231 cells compared to its parent hecogenin at the equal concentration.

Keywords

Anti-metastasis; Apoptosis; Hecogenin; Thiosemicarbazone and semicarbazone; Triple-negative breast cancer.

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