2. Academic Validation
  3. Synthesis and biological evaluation of diosgenin derivatives as potential anti-breast cancer agents

Synthesis and biological evaluation of diosgenin derivatives as potential anti-breast cancer agents

  • Bioorg Chem. 2025 Jul 26:164:108809. doi: 10.1016/j.bioorg.2025.108809.
Xiaoying Huang 1,  Di Wang 2,  Xinyu Shi 1,  Wenle Su 1,  Yilin Chen 1,  Yu Sun 1,  Tiancheng Ma 1,  Wenquan Zhu 1,  Qi Liu 1,  Liwei Ma 1,  Jia Sun 1,  Songjie Fan 1,  Yukun Ma 3,  Wenbao Wang 4,  Jinling Zhang 5
Affiliations

Affiliations

  • 1 Qiqihar Medical University, Qiqihar 161006, Heilongjiang, PR China.
  • 2 School of Life and Health Technology, Dongguan University of Technology, Dongguan 523808, Guangdong, PR China.
  • 3 Qiqihar Medical University, Qiqihar 161006, Heilongjiang, PR China. Electronic address: kuntengchongtian@163.com.
  • 4 Qiqihar Medical University, Qiqihar 161006, Heilongjiang, PR China. Electronic address: wangwenbao0824@163.com.
  • 5 Qiqihar Medical University, Qiqihar 161006, Heilongjiang, PR China. Electronic address: zhangjinling0413@163.com.
PMID: 40743710 DOI: 10.1016/j.bioorg.2025.108809
Abstract

Diosgenin (DSG) can function as a promising anti-tumor lead compound. However, its moderate anti-tumor efficacy limits its clinical applications. Herein, we report the design, synthesis, and evaluation of 24 DSG derivatives for their anti-breast Cancer activities in vitro. Their inhibitory activities against three different human breast Cancer cell lines (MDA-MB-231, MDA-MB-468, and MCF-7) and one normal human breast cell line (MCF-10A) were screened. The results indicated that compound 6j featuring 4-bromobenzyl exhibited remarkable inhibitory effects against MCF-7 cells (IC50 = 6.2 μM), with an IC50 value 7.95-fold lower than that of DSG (IC50 = 49.3 μM). Moreover, 6j exhibited relatively low toxicity against MCF-10A cells, indicating good selectivity. The mechanistic studies revealed that 6j significantly arrested MCF-7 cells in the G2/M phase, increased Reactive Oxygen Species accumulation, induced mitochondrial membrane potential depolarization, and triggered Apoptosis through the mitochondrial pathway. Therefore, 6j represents a promising anti-breast Cancer lead compound and warrants further investigation.

Keywords

1,2,3-Triazole; Anti-breast cancer; Apoptosis; Diosgenin derivatives.

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