Development of novel bis-pyrazole derivatives as antitumor agents with potent apoptosis induction effects and DNA damage

作者：Dai, Hong; Ge, Shushan; Guo, Jing; Chen, Shi; Huang, Meiling; Yang, Jiaying; Sun, Siyu; Ling, Yong^*; Shi, Yujun^*

来源：European Journal of Medicinal Chemistry, 2018, 143: 1066-1076.

DOI：10.1016/j.ejmech.2017.11.098

• Synthesis
• Antitumor agent
• Bis-pyrazole derivatives
• Apoptosis
• DNA damage

A series of bis-pyrazole derivatives were designed and synthesized, and their antitumor effects in vitro and in vivo were investigated. Several compounds displayed good antiproliferative activity with IC50 values in low-micromolar range against three human cancer cell lines in vitro, superior to 5-FU. The most potent compound 10M selectively inhibited human hepatocellular carcinoma cells but not non-tumor liver cell proliferation in vitro, and significantly triggered SMMC-7721 cell apoptosis by cleavage of both PARP and caspase-3 in a concentration-dependent manner. Further study revealed that the potent activity in the cell growth inhibition and apoptosis induction effects of 10M were related to DNA damage and activation of the p53 signaling pathway. Moreover, 10M showed low acute toxicity to mice and significant growth inhibition of the hepatoma tumor in vivo.

• 出版日期2018-1-1
• 单位南通大学