Oxazole-Bridged Combretastatin A-4 Derivatives with Tethered Hydroxamic Acids: Structure⁻Activity Relations of New Inhibitors of HDAC and/or Tubulin Function.
Antineoplastic Agents
/ chemistry
Bibenzyls
/ chemistry
Binding Sites
Cell Cycle
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Dose-Response Relationship, Drug
Fluorescent Antibody Technique
Histone Deacetylase Inhibitors
/ chemistry
Humans
Hydrogen Bonding
Hydroxamic Acids
/ chemistry
Inhibitory Concentration 50
Microtubules
/ metabolism
Models, Molecular
Molecular Conformation
Molecular Structure
Oxazoles
/ chemistry
Protein Binding
Structure-Activity Relationship
Tubulin
/ chemistry
Tubulin Modulators
/ chemistry
anticancer agents
combretastatin A-4
histone deacetylase
oxazole
tubulin
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
17 Jan 2019
17 Jan 2019
Historique:
received:
21
12
2018
revised:
03
01
2019
accepted:
14
01
2019
entrez:
20
1
2019
pubmed:
20
1
2019
medline:
2
5
2019
Statut:
epublish
Résumé
New inhibitors of tubulin polymerization and/or histone deacetylase (HDAC) activity were synthesized by attaching alkyl tethered hydroxamic acid appendages of varying length to oxazole-bridged combretastatin A-4 analogous caps. While their antiproliferative and microtubule disrupting effect was most pronounced for derivatives with short spacers, HDAC inhibition was strongest for those with longer spacers. These findings were further supported by computational methods such as structure-based docking experiments exploring the target interactions of the derivatives with varying linkers. For instance, compounds featuring short four-atom spacers between cap and hydroxamic acid inhibited the growth of various cancer cell lines and human endothelial hybrid cells with IC
Identifiants
pubmed: 30658435
pii: ijms20020383
doi: 10.3390/ijms20020383
pmc: PMC6359144
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Bibenzyls
0
Histone Deacetylase Inhibitors
0
Hydroxamic Acids
0
Oxazoles
0
Tubulin
0
Tubulin Modulators
0
combretastatin
7O62J06F18
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : Scho 402/12-1
Organisme : Else-Kroener Fresenius Stiftung
ID : 2016-A47
Organisme : Bundesministerium für Bildung und Forschung
ID : 031A262C
Références
Nucleic Acids Res. 2000 Jan 1;28(1):235-42
pubmed: 10592235
J Antibiot (Tokyo). 2000 Oct;53(10):1191-200
pubmed: 11132966
Oncogene. 2001 Aug 9;20(35):4768-76
pubmed: 11521189
Jpn J Cancer Res. 2001 Dec;92(12):1300-4
pubmed: 11749695
Blood. 2002 Mar 15;99(6):2060-9
pubmed: 11877280
J Med Chem. 2002 Apr 11;45(8):1697-711
pubmed: 11931625
Proteins. 2002 Jun 1;47(4):409-43
pubmed: 12001221
Prostate. 2004 May 1;59(2):177-89
pubmed: 15042618
Cancer Cell. 2004 May;5(5):455-63
pubmed: 15144953
Anticancer Res. 2004 Mar-Apr;24(2B):539-45
pubmed: 15160991
Am J Pathol. 2004 Oct;165(4):1401-11
pubmed: 15466404
Clin Cancer Res. 2004 Oct 15;10(20):6962-8
pubmed: 15501975
J Hepatol. 2004 Dec;41(6):1008-16
pubmed: 15582135
J Biol Chem. 2006 May 12;281(19):13548-58
pubmed: 16533812
Nat Biotechnol. 2007 Jan;25(1):84-90
pubmed: 17211407
Oncogene. 2007 Feb 26;26(9):1351-6
pubmed: 17322921
Oncogene. 2007 Aug 13;26(37):5541-52
pubmed: 17694093
Clin Cancer Res. 2007 Dec 15;13(24):7237-42
pubmed: 18094401
Mol Oncol. 2007 Jun;1(1):19-25
pubmed: 19383284
J Med Chem. 2010 Sep 23;53(18):6595-602
pubmed: 20731355
J Biomed Biotechnol. 2011;2011:875824
pubmed: 21076528
Immunol Cell Biol. 2012 Jan;90(1):85-94
pubmed: 22124371
PLoS One. 2011;6(12):e29085
pubmed: 22194993
J Cell Sci. 2012 Apr 15;125(Pt 8):1855-64
pubmed: 22544950
PLoS One. 2012;7(9):e45045
pubmed: 23024790
Apoptosis. 2013 Jan;18(1):110-20
pubmed: 23161364
Int J Clin Pharmacol Ther. 2013 Jan;51(1):41-3
pubmed: 23259996
J Comput Aided Mol Des. 2013 Jan;27(1):15-29
pubmed: 23269578
J Med Chem. 2013 Mar 14;56(5):2016-28
pubmed: 23379567
Biologics. 2013;7:47-60
pubmed: 23459471
Oncol Rep. 2013 Jun;29(6):2451-8
pubmed: 23564200
Bioorg Med Chem. 2013 Jun 1;21(11):3240-4
pubmed: 23602523
ChemMedChem. 2014 Apr;9(4):847-54
pubmed: 24678059
Drugs. 2014 Sep;74(13):1543-54
pubmed: 25134672
Bioorg Med Chem. 2015 Feb 1;23(3):373-89
pubmed: 25564377
Iran J Pharm Res. 2014 Fall;13(4):1165-72
pubmed: 25587304
Cancer Chemother Pharmacol. 2015 Apr;75(4):691-700
pubmed: 25618416
Invest New Drugs. 2015 Jun;33(3):541-54
pubmed: 25678082
Molecules. 2015 Mar 02;20(3):3898-941
pubmed: 25738536
Eur J Med Chem. 2015 May 5;95:127-35
pubmed: 25805446
Drugs. 2015 Apr;75(6):695-704
pubmed: 25837990
Cytometry A. 2015 Aug;87(8):707-16
pubmed: 25892097
Exp Cell Res. 2015 Aug 15;336(2):263-75
pubmed: 26101158
J Med Chem. 2016 Feb 25;59(4):1455-70
pubmed: 26443078
J Chem Inf Model. 2016 Jan 25;56(1):1-5
pubmed: 26679290
Cancer Res. 1989 Dec 1;49(23):6566-71
pubmed: 2684395
Nat Commun. 2016 Apr 25;7:11262
pubmed: 27109927
Nat Chem Biol. 2016 Sep;12(9):741-7
pubmed: 27454933
Br J Clin Pharmacol. 2017 Feb;83(2):255-268
pubmed: 27620987
Curr Cancer Drug Targets. 2018;18(1):39-56
pubmed: 28176653
Bioorg Med Chem. 2017 Sep 1;25(17):4894-4903
pubmed: 28774574
Mol Cancer Ther. 2017 Nov;16(11):2364-2374
pubmed: 28838999
J Immunol Methods. 1983 Dec 16;65(1-2):55-63
pubmed: 6606682
Cancer Res. 1983 Sep;43(9):3998-4006
pubmed: 6871841
J Comput Aided Mol Des. 1996 Feb;10(1):41-54
pubmed: 8786414