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
  • 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: [email protected].
  • 4. Qiqihar Medical University, Qiqihar 161006, Heilongjiang, PR China. Electronic address: [email protected].
  • 5. Qiqihar Medical University, Qiqihar 161006, Heilongjiang, PR China. Electronic address: [email protected].
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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