Discovery of indoline derivatives that inhibit esophageal squamous cell carcinoma growth by Noxa mediated apoptosis

  • Bioorg Chem. 2019 Nov;92:103190. doi: 10.1016/j.bioorg.2019.103190.
Dong-Jun Fu  1 ,  Miaomiao Li  2 ,  Sai-Yang Zhang  3 ,  Jiang-Feng Li  2 ,  Beibei Sha  2 ,  Longhao Wang  2 ,  Yan-Bing Zhang  4 ,  Ping Chen  5 ,  Tao Hu  6
Affiliations
  • 1. School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China; New Drug Research & Development Center, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001, China.
  • 2. School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • 3. School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China; Henan Institutes of Advanced Technology, Zhengzhou University, Zhengzhou 450001, China.
  • 4. New Drug Research & Development Center, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001, China.
  • 5. School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China; Henan Institutes of Advanced Technology, Zhengzhou University, Zhengzhou 450001, China. Electronic address: [email protected].
  • 6. School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China. Electronic address: [email protected].
PMID: 31465969 DOI: 10.1016/j.bioorg.2019.103190
Abstract

A series of novel indoline derivatives were synthesized and evaluated for antiproliferative activity against four selected Cancer cell lines (Hela, A549, HepG2 and KYSE30). Among them, compound 20 displayed the potent inhibition activity against esophageal Cancer cells (Kyse30, Kyse450, Kyse510 and EC109). Cellular mechanism studies in esophageal squamous cell carcinoma (ESCC) cells elucidated compound 20 inhibited cell growths in vitro and in vivo, reduced colony formation, arrested cell cycle at M phase, and induced Noxa-dependent Apoptosis in ESCC. Importantly, compound 20 was identified as a novel Noxa mediated Apoptosis Inducer. These results suggested that compound 20 might be a promising Anticancer agent with potential for development of further clinical applications.

Keywords
Cell growths in vitro and in vivo; Esophageal squamous cell carcinoma; Indoline; Noxa-dependent apoptosis.
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