Simple di- and trivanillates exhibit cytostatic properties toward cancer cells resistant to pro-apoptotic stimuli.
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.
Lamoral-Theys
Delphine
D
Institut de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium.
Pottier
Laurent
L
Kerff
Frédéric
F
Dufrasne
François
F
Proutière
Fabien
F
Wauthoz
Nathalie
N
Neven
Philippe
P
Ingrassia
Laurent
L
Antwerpen
Pierre Van
PV
Lefranc
Florence
F
Gelbcke
Michel
M
Pirotte
Bernard
B
Kraus
Jean-Louis
JL
Nève
Jean
J
Kornienko
Alexander
A
Kiss
Robert
R
Dubois
Jacques
J
D017209:Apoptosis / Q000187:drug effects; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors; D054697:Cytostatic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D014641:Vanillic Acid / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use
D018797:Cell Cycle Proteins; D054697:Cytostatic Agents; D009687:Nuclear Proteins; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D014641:Vanillic Acid
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