Advances in the 1-phenanthryl-tetrahydroisoquinoline series of PAK4 inhibitors: potent agents restrain tumor cell growth and invasion
Advances in the 1-phenanthryl-tetrahydroisoquinoline series of PAK4 inhibitors: potent agents restrain tumor cell growth and invasion
复制标题
1-菲基-四氢异喹啉系列PAK4抑制剂研究进展：有效抑制肿瘤细胞生长和侵袭
DOI：
10.1039/c6ob01072e
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发表时间：
2016-01-01
影响因子：
3.2
通讯作者：
Zhao, Dongmei
中科院分区：
文献类型：
--
作者：
Hao, Chenzhou;Li, Xiaodong;Zhao, Dongmei
A new series of novel 1-phenanthryl-tetrahydroisoquinoline derivatives were designed, synthesized and biologically evaluated for their PAK4 inhibitory activities and anti-proliferative effects against three cancer cell lines A549, MCF-7 and HT-1080. Among them, compound 12a exhibited the most potent inhibitory activity against PAK4 with an IC50 value of 0.42 mu M. Moreover, this compound inhibited the invasion of A549 tumor cells by regulating the PAK4-LIMK1-cofilin signaling pathway in vitro, and exhibited anti-tumor activity in vivo in the A549 tumor xenograft model. To further evaluate the binding mode of 12a with PAK4, the biotinylated 12a derivative has been synthesized and it was used for immunoprecipitation assay. Intriguingly, our observations suggest that 12a interacts with both the N- and C-termini of PAK4.
