2. Academic Validation
  3. Design, synthesis and biological evaluation of novel β-carbolines as antitumor agents via targeting autophagy in colorectal cancer

Design, synthesis and biological evaluation of novel β-carbolines as antitumor agents via targeting autophagy in colorectal cancer

  • Eur J Med Chem. 2025 Feb 5:283:117145. doi: 10.1016/j.ejmech.2024.117145.
Jingsheng Ao 1,  Chengyao Lai 2,  Xiaofei Wu 3,  Zhiyong Chen 2,  Weijie Yang 2,  Liqin Qiu 2,  Xiangpan Li 4,  Rihui Cao 5
Affiliations

Affiliations

  • 1 Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, 430072, PR China.
  • 2 School of Chemistry, Sun Yat-sen University, Guangzhou, 510275, PR China.
  • 3 Department of Neurology, Central War Zone General Hospital of the Chinese People's Liberation Army, Wuhan, 430072, PR China.
  • 4 Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, 430072, PR China. Electronic address: rm001227@whu.edu.cn.
  • 5 School of Chemistry, Sun Yat-sen University, Guangzhou, 510275, PR China. Electronic address: caorihui@mail.sysu.edu.cn.
PMID: 39653623 DOI: 10.1016/j.ejmech.2024.117145
Abstract

A series of novel β-carbolines with a flexible amino side chain at positions 1 and 3, respectively, were designed, synthesized and evaluated as potential antitumor agents. The results revealed that most of the compounds exhibited a broad spectrum of antiproliferative activity with IC50 value lower than 20 μM against human tumor cell lines. Among them, compound 2f was the most potent antiproliferative agent with IC50 value below 5.0 μM against human tumor cell lines. Subsequent studies on the in vivo antitumor efficacy of the representative compound 2f demonstrated its ability to hinder tumor progression and significantly diminish tumor mass in a mouse model of colorectal Cancer. Further investigation on mechanisms of action showed that compound 2f induced Autophagy via the ATG5/Atg7 pathway in HCT116 cells. These compounds may contribute to the development of therapeutic agents for colorectal Cancer.

Keywords

Antitumor; Autophagy; Synthesis; β-carbolines.

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