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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Barbiturates / chemical synthesis
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Barbiturates / chemistry
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Barbiturates / pharmacology*
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Dose-Response Relationship, Drug
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Humans
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Hydrazones / chemical synthesis
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Hydrazones / chemistry
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Hydrazones / pharmacology*
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Models, Molecular
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Molecular Structure
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Ribosomal Protein S6 Kinases, 90-kDa / antagonists & inhibitors*
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Ribosomal Protein S6 Kinases, 90-kDa / metabolism
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Structure-Activity Relationship
Substances
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Barbiturates
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Hydrazones
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Protein Kinase Inhibitors
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Ribosomal Protein S6 Kinases, 90-kDa
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barbituric acid