1. Potent hydrazone derivatives targeting esophageal cancer cells.
- Author
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Li, Ling-Yu, Peng, Jia-Di, Zhou, Wenjuan, Qiao, Hui, Deng, Xin, Li, Zhou-Hua, Li, Ji-Deng, Fu, Yun-Dong, Li, Song, Sun, Kai, Liu, Hong-Min, and Zhao, Wen
- Subjects
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HYDRAZONE derivatives , *CANCER cells , *APOPTOSIS , *CYTOMETRY , *CHEMICAL synthesis - 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 IC 50 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. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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