Abstract
A series of 33 novel divanillates and trivanillates were synthesized and found to possess promising cytostatic rather than cytotoxic properties. Several compounds under study decreased by >50% the activity of Aurora A, B, and C, and WEE1 kinase activity at concentrations <10% of their IC(50) growth inhibitory ones, accounting, at least partly, for their cytostatic effects in cancer cells and to a lesser extent in normal cells. Compounds 6b and 13c represent interesting starting points for the development of cytostatic agents to combat cancers, which are naturally resistant to pro-apoptotic stimuli, including metastatic malignancies.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Aurora Kinases
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Cell Cycle Proteins / antagonists & inhibitors
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Cytostatic Agents / chemical synthesis*
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Cytostatic Agents / pharmacology
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Inhibitory Concentration 50
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Neoplasms / drug therapy*
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Neoplasms / pathology
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Nuclear Proteins / antagonists & inhibitors
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Structure-Activity Relationship
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Vanillic Acid / chemical synthesis*
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Vanillic Acid / pharmacology
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Vanillic Acid / therapeutic use
Substances
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Cell Cycle Proteins
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Cytostatic Agents
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Nuclear Proteins
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Protein-Tyrosine Kinases
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WEE1 protein, human
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Aurora Kinases
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Protein Serine-Threonine Kinases
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Vanillic Acid