Design, synthesis and preliminary biological evaluation of N-hydroxy-4-(3-phenylpropanamido)benzamide (HPPB) derivatives as novel histone deacetylase inhibitors

被引：27

作者：

Jiao, Jie ^{[1
]}

Fang, Hao ^{[1
]}

Wang, Xuejian ^{[1
]}

Guan, Peng ^{[1
]}

Yuan, Yumei ^{[1
]}

Xu, Wenfang ^{[1
]}

机构：

[1] Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Jinan 250012, Shandong, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 11期

关键词：

HPPB; N-Hydroxybenzamide; Histone deacetylase inhibitors; Anticancer agents; Cell-cycle arrest; DIFFERENTIATION; TRICHOSTATIN; INDUCERS; AGENTS;

D O I：

10.1016/j.ejmech.2009.06.010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of N-hydroxy-4-(3-phenylpropanamido)benzamide (HPPB) derivatives comprising N-hydroxybenzamide group as zinc-chelating moiety were designed, synthesized and evaluated for their ability to inhibit histone deacetylases. These compounds possessed inhibitory activity against the enzymes with IC50 values as low as 4.0 mu M. Among them, the thiophene substituted derivative 5j (IC50 = 0.3 mu M) and benzo[d][1,3]dioxole derivative 5t (IC50 = 0.4 mu M) exhibited good antiproliferative activity against the growth of human colon carcinoma cell line HCT116 and non-small cell lung cancer cell (NSCLC) line A549. In addition, they were found to potently induce cell-cycle arrest at G2 phase. (C) 2009 Elsevier Masson SAS. All rights reserved.

引用

页码：4470 / 4476

页数：7

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