Exploration of 1-(3-chloro-4-(4-oxo-4H-chromen-2-yl)phenyl)-3-phenylurea derivatives as selective dual inhibitors of Raf1 and JNK1 kinases for anti-tumor treatment
作者： Feng Jin , Dan Gao , Cunlong Zhang , Feng Liu , Bizhu Chu
DOI: 10.1016/J.BMC.2012.04.006
关键词: Antitumor activity 、 Binding domain 、 Stereochemistry 、 Hepg2 cells 、 Phenylurea Derivatives 、 Urea 、 Chemistry 、 Flavones 、 Kinase 、 Toxicity
摘要: Abstract Based on the roles of Raf1 and JNK1 in hepatocarcinoma development, scaffold-based drug design was employed to produce a series compounds, which subsequently were synthesized explored as potential dual inhibitors kinases for anti-tumor treatment. The compound 1-(3-chloro-4-(6-ethyl-4-oxo-4 H -chromen-2-yl)phenyl)-3-(4-chloro-phenyl)urea ( 3d ) showed 66%, 67% 13% inhibition rate at 50 μM against Raf1, p38-alpha, respectively, but no effect ERK1 ERK2, inhibited expression pERK1/2 markedly HepG2 cells proliferation with IC 50 8.3 μM. Furthermore, lower toxicity normal liver cell-lines QSG7701 HL7702. Molecular docking study further that can fit into binding domain Raf1. Our data suggested activities associated kinases.
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