Abstract
Polo-like kinase 1 is an important and attractive oncological target that plays a key role in mitosis and cytokinesis. A combined pharmacophore- and docking-based virtual screening was performed to identify novel polo-like kinase 1 inhibitors. A total of 34 hit compounds were selected and tested in vitro, and some compounds showed inhibition of polo-like kinase 1 and human tumor cell growth. The most potent compound (66) inhibited polo-like kinase 1 with an IC(50) value of 6.99 μm. The docked binding models of two hit compounds were discussed in detail. These compounds contained novel chemical scaffolds and may be used as foundations for the development of novel classes of polo-like kinase 1 inhibitors.
© 2012 John Wiley & Sons A/S.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / pharmacology*
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Cell Cycle Proteins / antagonists & inhibitors*
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Cell Cycle Proteins / metabolism
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Drug Design*
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Humans
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Inhibitory Concentration 50
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Models, Molecular
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Neoplasms / drug therapy
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Neoplasms / enzymology
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Neoplasms / metabolism
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Polo-Like Kinase 1
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology*
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / antagonists & inhibitors*
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Proto-Oncogene Proteins / metabolism
Substances
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Antineoplastic Agents
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Cell Cycle Proteins
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins
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Protein Serine-Threonine Kinases