Abstract
We synthesized a series of vanillin-derived compounds and analyzed them in HeLa cells for their effects on the proliferation of cancer cells. The molecules are derivatives of the lead compound SBE13, a potent inhibitor of the inactive conformation of human polo-like kinase 1 (Plk1). Some of the new designs were able to inhibit cancer cell proliferation to a similar extent as the lead structure. Two of the compounds ((({4-[(6-chloropyridin-3-yl)methoxy]-3-methoxyphenyl}methyl)(pyridin-4-ylmethyl)amine) and (({4-[(4-chlorophenyl)methoxy]-3-methoxyphenyl}methyl)(pyridin-4-ylmethyl)amine)) were much stronger in their capacity to reduce HeLa cell proliferation and turned out to potently induce apoptosis and reduce Plk1 kinase activity in vitro.
Keywords:
Antiproliferative compounds; Cell cycle; Polo-like kinase 1.
Copyright © 2014. Published by Elsevier Ltd.
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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Apoptosis / drug effects
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Benzaldehydes / chemistry*
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Benzaldehydes / metabolism
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Benzaldehydes / pharmacology*
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Cell Cycle Checkpoints / drug effects
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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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HeLa Cells
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Humans
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Polo-Like Kinase 1
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Protein Binding
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Protein Isoforms / antagonists & inhibitors
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Protein Isoforms / metabolism
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / metabolism
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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*
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Benzaldehydes
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Cell Cycle Proteins
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Protein Isoforms
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins
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vanillin
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Protein Serine-Threonine Kinases