Abstract
The design and synthesis of a small library of 8-amidoflavone, 8-sulfonamidoflavone, 8-amido-7-hydroxyflavone, and heterocyclic analogues of flavopiridol is reported. The potential activity of these compounds as kinase inhibitors was evaluated by cytotoxicity studies in MCF-7 and ID-8 cancer cell lines and inhibition of CDK2-Cyclin A enzyme activity in vitro. The antiproliferative and CDK2-Cyclin A inhibitory activity of these analogues was significantly lower than the activity of flavopiridol. Molecular docking simulations were carried out and these studies suggested a different binding orientation inside the CDK2 binding pocket for these analogues compared to flavopiridol.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adenosine Triphosphate / chemistry
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology*
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Binding Sites
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Chromatography, Thin Layer
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Cyclin A / antagonists & inhibitors*
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Cyclin-Dependent Kinase 2 / antagonists & inhibitors*
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Flavonoids / chemical synthesis*
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Flavonoids / pharmacology*
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Hydrogen Bonding
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Indicators and Reagents
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Magnetic Resonance Spectroscopy
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Models, Molecular
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Piperidines / chemical synthesis*
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Piperidines / pharmacology*
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Spectrometry, Mass, Fast Atom Bombardment
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Cyclin A
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Enzyme Inhibitors
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Flavonoids
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Indicators and Reagents
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Piperidines
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alvocidib
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Adenosine Triphosphate
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Cyclin-Dependent Kinase 2