Abstract
Harmine (3), 7-fluoro-1-methyl beta-carboline (35) and 1-(5-methyl-imidazol-4-yl) beta-carboline (41) were potent and specific inhibitors of cyclin-dependent kinases. The degree of aromaticity of the tricyclic ring and the positioning of substituents are important for inhibitory activity. While most beta-carbolines inhibited CDK2 and CDK5 to the same extent, selective inhibition against CDK2 was observed in 1-(2-chlorophenyl)- (12), 1-(2-fluorophenyl)- (15), and 1-(2-chloro-5-nitrophenyl)- (28) beta-carbolines.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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CDC2-CDC28 Kinases*
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Carbolines / pharmacology*
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase 5
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclin-Dependent Kinases / antagonists & inhibitors*
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Cyclins / pharmacology*
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
Substances
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Carbolines
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Cyclin-Dependent Kinase 5
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Protein Serine-Threonine Kinases
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CDC2-CDC28 Kinases
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases