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Triazole and Benzotriazole Derivatives as Novel Inhibitors for p90 Ribosomal S6 Protein Kinase 2: Synthesis, Molecular Docking and SAR Analysis
Author(s) -
Yuan Jun,
Zhong Ye,
Li Shiliang,
Zhao Xue,
Luan Guoqin,
Zhao Zhenjiang,
Huang Jin,
Li Honglin,
Xu Yufang
Publication year - 2013
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.201300443
Subject(s) - chemistry , benzotriazole , docking (animal) , stereochemistry , enzyme , active site , triazole , in vitro , ribosomal protein , combinatorial chemistry , biochemistry , ribosome , organic chemistry , medicine , rna , nursing , gene
A series of triazole and benzotriazole derivatives as novel p90 ribosomal S6 protein kinase 2 (RSK2) inhibitors were designed and synthesized. The in vitro activities against RSK2 were evaluated, and among 14 compounds, compounds 5 , 6 , 11 , 12 , 13 and 14 exhibited enzyme IC 50 values of 8.91, 2.86, 3.19, 3.05, 4.49 and 2.09 µmol/L respectively. The proposed binding modes were simulated using molecular docking method, and the docking results coupled with the structure‐activity relationship (SAR) analysis indicated that all these active compounds bound to the RSK2 ATP binding site at NTKD, and the electron‐donating groups on the 4‐position of phenyl were the determinant point for the inhibitory activity.