2. Academic Validation
  3. Discovery of novel urea derivatives as ferroptosis and autophagy inducer for human colon cancer treatment

Discovery of novel urea derivatives as ferroptosis and autophagy inducer for human colon cancer treatment

  • Eur J Med Chem. 2024 Feb 24:268:116277. doi: 10.1016/j.ejmech.2024.116277.
Tingting Liang 1,  Haiyang Dong 1,  Zhuangzhuang Wang 1,  Lu Lu 1,  Xueting Song 1,  Jianguo Qi 1,  Yahong Zhang 2,  Jianhong Wang 3,  Guanhua Du 4
Affiliations

Affiliations

  • 1 Key Laboratory of Natural Medicine and Immune-Engineering of Henan Province, Henan University, Kaifeng, 475004, Henan, China.
  • 2 Key Laboratory of Natural Medicine and Immune-Engineering of Henan Province, Henan University, Kaifeng, 475004, Henan, China. Electronic address: [email protected].
  • 3 Key Laboratory of Natural Medicine and Immune-Engineering of Henan Province, Henan University, Kaifeng, 475004, Henan, China; Huaihe Hospital of Henan University, Kaifeng, 475004, Henan, China. Electronic address: [email protected].
  • 4 Key Laboratory of Natural Medicine and Immune-Engineering of Henan Province, Henan University, Kaifeng, 475004, Henan, China; School of Pharmacy, Henan University, Kaifeng, 475004, Henan, China. Electronic address: [email protected].
PMID: 38422700 DOI: 10.1016/j.ejmech.2024.116277
Abstract

A series of novel urea derivatives were designed, synthesized and evaluated for their inhibitory activities against HT-29 cells, and structure-activity relationships (SAR) were summarized. Compound 10p stood out from these derivatives, exhibiting the most potent antiproliferative activity. Further biological studies demonstrated that 10p arrested cell cycle at G2/M phase via regulating cell cycle-related proteins CDK1 and Cyclin B1. The underlying molecular mechanisms demonstrated that 10p induced cell death through Ferroptosis and Autophagy, but not Apoptosis. Moreover, 10p-induced Ferroptosis and Autophagy were both related with accumulation of ROS, but they were independent of each other. Our findings substantiated that 10p combines Ferroptosis induction and Autophagy trigger in single molecule, making it a potential candidate for colon Cancer treatment and is worth further development.

Keywords

Autophagy; Colon cancer; Ferroptosis; Urea derivatives.

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