Abstract
Based on our previous experiences with synthesis of purines, novel 2,6,9-trisubstituted purine derivatives were prepared and assayed for the ability to inhibit CDK1/cyclin B kinase. One of newly synthesized compounds designated as olomoucine II, 6-[(2-hydroxybenzyl)amino]-2-[[1-(hydroxymethyl)propyl]amino]-9-isopropylpurine, displays 10 times higher inhibitory activity than roscovitine, potent and specific CDK1 inhibitor. Olomoucine II in vitro cytotoxic activity exceeds purvalanol A, the most potent CDK inhibitor, as it kills the CEM cells with IC(50) value of 3.0 microM.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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CDC2 Protein Kinase / antagonists & inhibitors
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CDC28 Protein Kinase, S cerevisiae / antagonists & inhibitors
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Cell Survival / drug effects
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology
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Humans
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Kinetin
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Purines / chemical synthesis*
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Purines / pharmacology*
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Roscovitine
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Structure-Activity Relationship
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Tumor Cells, Cultured
Substances
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6-((3-chloro)anilino)-2-(isopropyl-2-hydroxyethylamino)-9-isopropylpurine
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Antineoplastic Agents
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Enzyme Inhibitors
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Purines
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olomoucine II
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Roscovitine
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olomoucine
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CDC2 Protein Kinase
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CDC28 Protein Kinase, S cerevisiae
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Kinetin