Rational design and diversity-oriented synthesis of peptoid-based selective HDAC6 inhibitors

被引：45

作者：

Diedrich, D. ^{[1
]}

Hamacher, A. ^{[1
]}

Gertzen, C. G. W. ^{[1
]}

Avelar, L. A. Alves ^{[1
]}

Reiss, G. J. ^{[2
]}

Kurz, T. ^{[1
]}

Gohlke, H. ^{[1
]}

Kassack, M. U. ^{[1
]}

Hansen, F. K. ^{[1
]}

机构：

[1] Univ Dusseldorf, Inst Pharmazeut & Med Chem, Univ Str 1, D-40225 Dusseldorf, Germany

[2] Univ Dusseldorf, Inst Anorgan Chem & Strukturchem, Univ Str 1, D-40225 Dusseldorf, Germany

来源：

CHEMICAL COMMUNICATIONS | 2016年 / 52卷 / 15期

关键词：

DEACETYLASE; 6; INHIBITORS; HISTONE DEACETYLASES; TUBASTATIN; ENZYMES; DOCKING; CANCER; CELLS; ACID;

D O I：

10.1039/c5cc10301k

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A mini library of HDAC inhibitors with peptoid-based cap groups was synthesized using an efficient multicomponent approach. Four compounds were identified as potent HDAC6 inhibitors with a selectivity over other HDAC isoforms. The most potent HDAC6 inhibitor revealed remarkable chemosensitizing properties and completely reverted the cisplatin resistance in Cal27 CisR cells.

引用

页码：3219 / 3222

页数：4

共 21 条

[1] Selective Histone Deacetylase 6 Inhibitors Bearing Substituted Urea Linkers Inhibit Melanoma Cell Growth [J].

Bergman, Joel A. ;

Woan, Karrune ;

Perez-Villarroel, Patricio ;

Villagra, Alejandro ;

Sotomayor, Eduardo M. ;

Kozikowski, Alan P. .

JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (22) :9891-9899

[2] Inside HDAC with HDAC inhibitors [J].

Bertrand, Philippe .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2010, 45 (06) :2095-2116

[3] Epigenetics - An epicenter of gene regulation: Histones and histone-modifying enzymes [J].

Biel, M ;

Wascholowski, V ;

Giannis, A .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2005, 44 (21) :3186-3216

[4] Chemical phylogenetics of histone deacetylases [J].

Bradner, James E. ;

West, Nathan ;

Grachan, Melissa L. ;

Greenberg, Edward F. ;

Haggarty, Stephen J. ;

Warnow, Tandy ;

Mazitschek, Ralph .

NATURE CHEMICAL BIOLOGY, 2010, 6 (03) :238-243

[5] Rational Design and Simple Chemistry Yield a Superior, Neuroprotective HDAC6 Inhibitor, Tubastatin A [J].

Butler, Kyle V. ;

Kalin, Jay ;

Brochier, Camille ;

Vistoli, Guilio ;

Langley, Brett ;

Kozikowski, Alan P. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2010, 132 (31) :10842-10846

[6] Potent and selective HDAC6 inhibitory activity of N-(4-hydroxycarbamoylbenzyl)-1,2,4,9-tetrahydro-3-thia-9-azafluorenes as novel sulfur analogues of Tubastatin A [J].

De Vreese, Rob ;

Verhaeghe, Tom ;

Desmet, Tom ;

D'hooghe, Matthias .

CHEMICAL COMMUNICATIONS, 2013, 49 (36) :3775-3777

[7] Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders [J].

Falkenberg, Katrina J. ;

Johnstone, Ricky W. .

NATURE REVIEWS DRUG DISCOVERY, 2014, 13 (09) :673-691

[8] Synthesis, Biological Evaluation, and Molecular Docking of Ugi Products Containing a Zinc-Chelating Moiety as Novel Inhibitors of Histone Deacetylases [J].

Grolla, Ambra A. ;

Podesta, Valeria ;

Chini, Maria Giovanna ;

Di Micco, Simone ;

Vallario, Antonella ;

Genazzani, Armando A. ;

Canonico, Pier Luigi ;

Bifulco, Giuseppe ;

Tron, Gian Cesare ;

Sorba, Giovanni ;

Pirali, Tracey .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (09) :2776-2785

[9] HDAC inhibitors still need a home run, despite recent approval [J].

Guha, Malini .

NATURE REVIEWS DRUG DISCOVERY, 2015, 14 (04) :226-227

[10] Inhibitors selective for HDAC6 in enzymes and cells [J].

Gupta, Praveer K. ;

Reid, Robert C. ;

Liu, Ligong ;

Lucke, Andrew J. ;

Broomfield, Steve A. ;

Andrews, Melanie R. ;

Sweet, Matthew J. ;

Fairlie, David P. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (23) :7067-7070

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