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Journal of Enzyme Inhibition and Medicinal Chemistry Volume 28, 2013 - Issue 4
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Research Article

Synthesis, activity evaluation, and docking analysis of barbituric acid aryl hydrazone derivatives as RSK2 inhibitors

Mengzhu XueShanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai, China
,
Minghao XuShanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai, China
,
Weiqiang LuShanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai, China
,
Jin HuangShanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai, China
,
Honglin LiShanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai, China
,
Yufang XuShanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai, China
,
Xiaofeng LiuShanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai, China
&
Zhenjiang ZhaoShanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai, China
 show all
Pages 747-752 | Received 31 Dec 2011, Accepted 27 Mar 2012, Published online: 30 Apr 2012
 
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Abstract

The 90 kDa ribosomal S6 kinases (RSKs), especially RSK2, have attracted attention for the development of new anticancer agents. Through structural optimization of the hit compound 1 from our previous study, a series of barbituric acid aryl hydrazone analogues were designed and synthesized as potential RSK2 inhibitors. The most potent one, compound 9, showed a higher activity against RSK2 with an IC50 value of 1.95 μM. To analyze and elucidate their structure-activity relationship, the homology model of RSK2 N-terminal kinase domain was built and molecular docking simulations were performed, which provide helpful clues to design new inhibitors with desired activities.

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