期刊
CHEMICAL BIOLOGY & DRUG DESIGN
卷 94, 期 1, 页码 1368-1377出版社
WILEY
DOI: 10.1111/cbdd.13514
关键词
anti-lung cancer; apoptosis; NF-kappa B inhibitor; pyroptosis; toxicity
资金
- ZheJiang Province Natural Science Fund of China [LY15H160062, LY15H280014, LY17H160059]
- National Natural Science Foundation of China [81703766]
- Opening Project of Zhejiang Provincial Top Key Discipline of Pharmaceutical Sciences
- General Scientific Research Projects of Zhejiang Education Department [Y201839895]
As NF-kappa B signaling pathway is constitutively activated in lung cancer, targeting NF-kappa B has a potential for the treatment. EF24 has been proved to be a NF-kappa B inhibitor with good antitumor activity, while whose toxicity possibly became one of the obstacles to enter into clinical application. In order to find high efficiency and low toxicity NF-kappa B inhibitors, EF24 was modified and 13d was screened out. It was proved that 13d possessed an effective combination of inhibiting NF-kappa B pathway and showing lower cytotoxicity on normal cells as well as less toxicity in acute toxicity experiment compared with the lead compound of EF24. In addition, 13d was found to inhibit cell vitality, arrest cell cycle in G2/M phase, promote cell apoptosis, and suppress the xenograft tumor growth. Furthermore, 13d was elucidated to induce pyroptosis developing from apoptosis, which was associated with the inhibition of NF-kappa B. Taken together, it was suggested that 13d was a potent antitumor agent.
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