Identification of 4-hydroxyquinolines inhibitors of p300/CBP histone acetyltransferases

被引：74

作者：

Mai, Antonello ^{[1
]}

Rotili, Dante ^{[1
]}

Tarantino, Domenico ^{[1
]}

Nebbioso, Angela ^{[2
]}

Castellano, Sabrina ^{[3
]}

Sbardella, Gianluca ^{[3
]}

Tini, Marc ^{[4
]}

Altucci, Lucia ^{[2
]}

机构：

[1] Univ Roma La Sapienza, Dipartimento Chim & Tecnol Farm, Ist Pasteur Fdn Cenci Bolognetti, I-00185 Rome, Italy

[2] Univ Naples 2, Dipartimento Patol Gen, I-80138 Naples, Italy

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

[4] Univ Western Ontario, Schulich Sch Med & Dent, Siebens Drake Med Res Inst, Dept Physiol & Pharmacol, London, ON N6G 2V4, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 04期

基金：

芬兰科学院;

关键词：

Epigenetics; Chromatin remodeling; Histone acetyltransferase; 4-Hydroxyquinoline; Apoptosis; Cytodifferentiation; Histone acetylation; p300/CBP; DEACETYLASE SIRTUIN INHIBITORS; SMALL-MOLECULE MODULATORS; GLOBAL GENE-EXPRESSION; ACUTE MYELOID-LEUKEMIA; BIOLOGICAL EVALUATION; HISTONE/PROTEIN METHYLTRANSFERASE; CHROMATIN TRANSCRIPTION; REPRESSES; CANCER; ACETYLATION;

D O I：

10.1016/j.bmcl.2008.12.097

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We identified a series of 4-hydroxyquinolines bearing a C1 to C15 alkyl chain at the C2 position and a carbethoxy/carboxy group at the C3 position of the quinoline nucleus (MC compounds), endowed with selective inhibitory activity against the p300/CBP HAT enzymes. Enzyme inhibition was investigated using in vitro HAT assays and by western blot analysis of cellular lysates to examine the acetylation levels of histone H3 and alpha-tubulin. When tested in U937 cells, some compounds displayed pro-apoptotic or cytodifferentiating properties. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：1132 / 1135

页数：4

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