2. Academic Validation
  3. Potent hydrazone derivatives targeting esophageal cancer cells

Potent hydrazone derivatives targeting esophageal cancer cells

  • Eur J Med Chem. 2018 Mar 25:148:359-371. doi: 10.1016/j.ejmech.2018.02.033.
Ling-Yu Li 1,  Jia-Di Peng 1,  Wenjuan Zhou 1,  Hui Qiao 1,  Xin Deng 1,  Zhou-Hua Li 1,  Ji-Deng Li 1,  Yun-Dong Fu 1,  Song Li 1,  Kai Sun 2,  Hong-Min Liu 3,  Wen Zhao 4
Affiliations

Affiliations

  • 1 Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, PR China.
  • 2 Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, PR China. Electronic address: kaisun@zzu.edu.cn.
  • 3 Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, PR China. Electronic address: liuhm@zzu.edu.cn.
  • 4 Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, PR China. Electronic address: zhaowen@zzu.edu.cn.
PMID: 29475156 DOI: 10.1016/j.ejmech.2018.02.033
Abstract

Hydrazone and their derivatives are a series of highly active molecules, which are widely used as lead compounds for the research and development of new anti-cancer drugs. In this study, 20 compounds were synthesized, based on this scaffold and their in vitro cytotoxicity against 6 Cancer cell lines, including EC9706, SMMC-7721, MCF7, PC3, MGC-803 and EC109 was tested. Among them, compound 6p, showed strong anti-proliferative activities on esophageal carcinoma cells: EC9706 and EC109 with IC50 values of 1.09 ± 0.03 and 2.79 ± 0.45 μM, respectively. 6p also significantly induces both EC9706 and EC109 cell cycle arrest at G0/G1 phase and cell Apoptosis, as well as intracellular ROS accumulation, which could be markedly reversed Caspase or ROS inhibitor: NAC. Meanwhile, treatment of compound 6p results in significant declined mitochondria membrane potential, increases in the expression of P53 and Bax, as well as decrease in Bcl-2. 6p also activates Caspase-8/9/3, PARP and Bid, indicating that 6p induces Cancer cell Apoptosis via the death receptor-mediated extrinsic pathway and the mitochondria-mediated intrinsic pathway. Further studies also proved that 6p does not show obvious side effects at cellular and in vivo levels. Our findings suggested that hydrazone derivative: compound 6p may serve as a lead compound for further optimization against esophageal Cancer cells.

Keywords

Apoptosis; Cell cycle arrest; Cytotoxicity; Hydrazone compounds.

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