Molecular modifications on carboxylic acid derivatives as potent histone deacetylase inhibitors: Activity and docking studies

被引：144

作者：

Bora-Tatar, Gamze ^{[2
]}

Dayangac-Erden, Didem ^{[2
]}

Demir, Ayhan S. ^{[3
]}

Dalkara, Sevim ^{[4
]}

Yelekci, Kemal ^{[1
]}

Erdem-Yurter, Hayat ^{[2
]}

机构：

[1] Kadir Has Univ, Fac Arts & Sci, Dept Stat & Comp Sci, TR-34083 Istanbul, Turkey

[2] Hacettepe Univ, Fac Med, Dept Med Biol, TR-06100 Ankara, Turkey

[3] Middle E Tech Univ, Fac Arts & Sci, Dept Chem, TR-06531 Ankara, Turkey

[4] Hacettepe Univ, Fac Pharm, Dept Pharmaceut Chem, TR-06100 Ankara, Turkey

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 14期

关键词：

HDAC inhibitors; Molecular docking; Caffeic acid derivatives; Chlorogenic acid; Curcumin; Carboxylic acid derivatives; SPINAL MUSCULAR-ATROPHY; HDAC INHIBITORS; HYDROXAMIC ACID; CANCER-THERAPY; CAFFEIC ACID; CURCUMIN; DYNAMICS; AGENTS;

D O I：

10.1016/j.bmc.2009.05.042

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In the light of known HDAC inhibitors, 33 carboxylic acid derivatives were tested to understand the structural requirements for HDAC inhibition activity. Several modifications were applied to develop the structure-activity relationships of carboxylic acid HDAC inhibitors. HDAC inhibition activities were investigated in vitro by using HeLa nuclear extract in a fluorimetric assay. Molecular docking was also carried out for the human HDAC8 enzyme in order to predict inhibition activity and the 3D poses of inhibitor-enzyme complexes. Of these compounds, caffeic acid derivatives such as chlorogenic acid and curcumin were found to be highly potent compared to sodium butyrate, which is a well-known HDAC inhibitor. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：5219 / 5228

页数：10

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