title: Simple di- and trivanillates exhibit cytostatic properties toward cancer cells resistant to pro-apoptotic stimuli.
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.
authors.affiliation: Institut de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Delphine
authors.initials: D
authors.lastname: Lamoral-Theys
authors.forename: Laurent
authors.initials: L
authors.lastname: Pottier
authors.forename: Frédéric
authors.initials: F
authors.lastname: Kerff
authors.forename: François
authors.initials: F
authors.lastname: Dufrasne
authors.forename: Fabien
authors.initials: F
authors.lastname: Proutière
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wauthoz
authors.forename: Philippe
authors.initials: P
authors.lastname: Neven
authors.forename: Laurent
authors.initials: L
authors.lastname: Ingrassia
authors.forename: Pierre Van
authors.initials: PV
authors.lastname: Antwerpen
authors.forename: Florence
authors.initials: F
authors.lastname: Lefranc
authors.forename: Michel
authors.initials: M
authors.lastname: Gelbcke
authors.forename: Bernard
authors.initials: B
authors.lastname: Pirotte
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Kraus
authors.forename: Jean
authors.initials: J
authors.lastname: Nève
authors.forename: Alexander
authors.initials: A
authors.lastname: Kornienko
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
authors.forename: Jacques
authors.initials: J
authors.lastname: Dubois
mesh_terms: 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
chemical_list: 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
references.citation: Curr Med Chem. 2009;16(24):3081-92
references.pmid: 19689285
references.citation: Curr Drug Discov Technol. 2009 Jun;6(2):103-34
references.pmid: 19519337
references.citation: J Med Chem. 2009 Feb 26;52(4):1100-14
references.pmid: 19199649
references.citation: Planta Med. 2002 May;68(5):445-8
references.pmid: 12058323
references.citation: Eur J Pharm Sci. 2005 May;25(1):57-65
references.pmid: 15854801
references.citation: Expert Opin Emerg Drugs. 2009 Jun;14(2):299-310
references.pmid: 19519286
references.citation: Nat Clin Pract Oncol. 2009 Jan;6(1):43-52
references.pmid: 18982000
references.citation: J Cell Mol Med. 2009 Sep;13(9B):3960-72
references.pmid: 19243476
references.citation: Cancer. 2002 Aug 1;95(3):641-55
references.pmid: 12209758
references.citation: Curr Opin Oncol. 2009 Jul;21(4):374-80
references.pmid: 19412097
references.citation: Nat Rev Drug Discov. 2004 Dec;3(12):1001-10
references.pmid: 15573099
references.citation: J Agric Food Chem. 2009 Apr 22;57(8):3055-63
references.pmid: 19368348
references.citation: Nature. 2005 Oct 13;437(7061):942-3
references.pmid: 16222266
references.citation: Clin Sci (Lond). 2009 Aug 14;117(6):209-28
references.pmid: 19663810
references.citation: J Med Chem. 2009 May 28;52(10):3300-7
references.pmid: 19402633
references.citation: JAMA. 2004 Jul 28;292(4):419-22
references.pmid: 15280324
references.citation: J Med Chem. 2009 Oct 22;52(20):6244-56
references.pmid: 19788245
references.citation: Breast Cancer Res Treat. 2010 Jun;121(3):737-42
references.pmid: 19941161
references.citation: Mol Cell. 2003 Oct;12(4):851-62
references.pmid: 14580337
references.citation: J Comput Chem. 2007 Apr 30;28(6):1145-52
references.pmid: 17274016
references.citation: Neoplasia. 2007 Sep;9(9):766-76
references.pmid: 17898872
references.citation: Neuro Oncol. 2009 Aug;11(4):414-22
references.pmid: 19001526
references.citation: Biochem Pharmacol. 2008 Dec 1;76(11):1340-51
references.pmid: 18755156
references.citation: AAPS J. 2009 Sep;11(3):495-510
references.pmid: 19590964
references.citation: Cancer Treat Rev. 2009 Nov;35(7):597-607
references.pmid: 19660870
references.citation: Oncogene. 2003 May 19;22(20):3138-51
references.pmid: 12789290
references.citation: Mol Cancer Res. 2009 Jan;7(1):142-55
references.pmid: 19147545
references.citation: Chem Rev. 1996 Dec 19;96(8):3147-3176
references.pmid: 11848856
references.citation: Lab Invest. 2002 Feb;82(2):147-58
references.pmid: 11850528
references.citation: Mol Cancer Ther. 2009 Sep;8(9):2635-44
references.pmid: 19723887
references.citation: Cancer Lett. 2008 Oct 8;269(2):226-42
references.pmid: 18492603
references.citation: Neoplasia. 2006 May;8(5):402-12
references.pmid: 16790089
references.citation: Oncogene. 2007 Sep 6;26(41):6071-81
references.pmid: 17667937
references.citation: J Med Chem. 1977 Nov;20(11):1388-93
references.pmid: 915898
references.citation: Cancer Res. 2006 Mar 1;66(5):2500-5
references.pmid: 16510563
references.citation: Mol Carcinog. 2006 Jun;45(6):409-15
references.pmid: 16652354
references.citation: Curr Med Chem. 2009;16(30):3943-65
references.pmid: 19747130
references.citation: Cancer Lett. 2008 Dec 18;272(2):177-85
references.pmid: 18579285
references.citation: Neoplasia. 2005 Apr;7(4):312-23
references.pmid: 15967108
references.citation: J Neurobiol. 1998 Nov 15;37(3):373-82
references.pmid: 9828043
references.citation: Trends Pharmacol Sci. 2005 Apr;26(4):178-82
references.pmid: 15808341
references.citation: Curr Med Chem. 2010;17(9):812-25
references.pmid: 20156174
references.citation: J Invest Dermatol. 2010 Jan;130(1):28-37
references.pmid: 19571822
references.citation: BMC Cancer. 2009 Oct 16;9:366
references.pmid: 19835603
references.citation: J Clin Oncol. 2005 Apr 1;23(10):2411-22
references.pmid: 15800333
references.citation: Oncologist. 2009 Aug;14(8):780-93
references.pmid: 19684075
references.citation: Curr Cancer Drug Targets. 2009 May;9(3):307-19
references.pmid: 19442051
references.citation: Cancer Res. 2009 Aug 1;69(15):6208-15
references.pmid: 19638587
references.citation: Cancer. 2004 Oct 15;101(8):1908-18
references.pmid: 15386340
references.citation: Nat Rev Cancer. 2009 Jun;9(6):429-39
references.pmid: 19472429
references.citation: Anticancer Agents Med Chem. 2007 Mar;7(2):171-88
references.pmid: 17348826
references.citation: Mol Cancer Ther. 2003 Mar;2(3):225-6
references.pmid: 12657716
references.citation: Chem Biol Drug Des. 2009 Jul;74(1):1-15
references.pmid: 19519739
references.citation: Curr Med Chem. 2009;16(16):1949-63
references.pmid: 19519375
references.citation: Chem Biol. 2008 Jun;15(6):552-62
references.pmid: 18559266
references.citation: J Cell Sci. 2003 Dec 15;116(Pt 24):4883-90
references.pmid: 14625382