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

被引：36

作者：

Grolla, Ambra A. ^{[2
,3
]}

Podesta, Valeria ^{[2
,3
]}

Chini, Maria Giovanna ^{[1
]}

Di Micco, Simone ^{[1
]}

Vallario, Antonella ^{[2
,3
]}

Genazzani, Armando A. ^{[2
,3
]}

Canonico, Pier Luigi ^{[2
,3
]}

Bifulco, Giuseppe ^{[1
]}

Tron, Gian Cesare ^{[2
,3
]}

Sorba, Giovanni ^{[2
,3
]}

Pirali, Tracey ^{[2
,3
]}

机构：

[1] Univ Salerno, Dipartimento Sci Farmaceut, I-84084 Fisciano, SA, Italy

[2] Univ Piemonte Orientale, Dipartimento Sci Chim Alimentari Farmaceut & Farm, I-28100 Novara, Italy

[3] Univ Piemonte Orientale, Drug & Food Biotechnol Ctr, I-28100 Novara, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 09期

关键词：

DESIGN; BINDING;

D O I：

10.1021/jm801529c

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

HDAC inhibitors show great promise for the treatment of cancer. AS part of a broader effort to explore the SAR of HDAC inhibitors, synthesis, biological evaluation, and molecular docking of novel Ugi products containing a zinc-chelating moiety are presented. One compound shows improved inhibitory potencies compared to SARA, demonstrating that hindered lipophilic residues grafted on the peptide scaffold of the alpha-aminoacylamides can be favorable in the interaction with the enzyme.

引用

页码：2776 / 2785

页数：10

共 27 条

[1]

[Anonymous], 2017, J MOL STRUCT, DOI DOI 10.1016/J.MOLSTRUC.2017.03.014

[2] Anticancer activities of histone deacetylase inhibitors [J].

Bolden, Jessica E. ;

Peart, Melissa J. ;

Johnstone, Ricky W. .

NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (09) :769-784

[3] DETERMINING ATOM-CENTERED MONOPOLES FROM MOLECULAR ELECTROSTATIC POTENTIALS - THE NEED FOR HIGH SAMPLING DENSITY IN FORMAMIDE CONFORMATIONAL-ANALYSIS [J].

BRENEMAN, CM ;

WIBERG, KB .

JOURNAL OF COMPUTATIONAL CHEMISTRY, 1990, 11 (03) :361-373

[4] Inhibitors of histone deacetylase (HDAC) restore the p53 pathway in neuroblastoma cells [J].

Condorelli, F. ;

Gnemmi, I. ;

Vallario, A. ;

Genazzani, A. A. ;

Canonico, P. L. .

BRITISH JOURNAL OF PHARMACOLOGY, 2008, 153 (04) :657-668

[5] Molecular modeling studies toward the structural optimization of new cyclopeptide-based HDAC inhibitors modeled on the natural product FR235222 [J].

Di Micco, Simone ;

Terracciano, Stefania ;

Bruno, Ines ;

Rodriquez, Manuela ;

Riccio, Raffaele ;

Taddei, Maurizio ;

Bifulco, Giuseppe .

BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (18) :8635-8642

[6]

Dömling A, 2000, ANGEW CHEM INT EDIT, V39, P3168, DOI 10.1002/1521-3773(20000915)39:18<3168::AID-ANIE3168>3.0.CO

[7]

2-U

[8] Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors [J].

Finnin M.S. ;

Donigian J.R. ;

Cohen A. ;

Richon V.M. ;

Rifkind R.A. ;

Marks P.A. ;

Breslow R. ;

Pavletich N.P. .

Nature, 1999, 401 (6749) :188-193

[9] Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin [J].

Furumai, R ;

Komatsu, Y ;

Nishino, N ;

Khochbin, S ;

Yoshida, M ;

Horinouchi, S .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (01) :87-92

[10]

Komatsu Y, 2001, CANCER RES, V61, P4459

← 1 2 3 →