Article

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

Shanghai 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.
Journal of Enzyme Inhibition and Medicinal Chemistry (impact factor: 1.62). 04/2012; DOI:10.3109/14756366.2012.681651
Source: PubMed

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 IC(50) 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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Keywords

90 kDa ribosomal S6 kinases
 
barbituric acid aryl hydrazone analogues
 
molecular docking simulations
 
new anticancer agents
 
potential RSK2 inhibitors
 
provide helpful clues
 
RSK2
 
RSK2 N-terminal kinase domain
 
structural optimization
 
structure-activity relationship
 
μM