Targeting epigenetic reader and eraser: Rational design, synthesis and in vitro evaluation of dimethylisoxazoles derivatives as BRD4/HDAC dual inhibitors

被引：54

作者：

Zhang, Zhimin ^{[1
]}

Hou, Shaohua ^{[1
]}

Chen, Hongli ^{[1
]}

Ran, Ting ^{[2
]}

Jiang, Fei ^{[1
]}

Bian, Yuanyuan ^{[1
]}

Zhang, Dewei ^{[1
]}

Zhi, Yanle ^{[1
]}

Wang, Lu ^{[1
]}

Zhang, Li ^{[1
]}

Li, Hongmei ^{[1
]}

Zhang, Yanmin ^{[2
]}

Tang, Weifang ^{[1
]}

Lu, Tao ^{[2
,3
]}

Chen, Yadong ^{[2
]}

机构：

[1] Sch Sci, Dept Organ Chem, 639 Longmian Ave, Nanjing 211198, Jiangsu, Peoples R China

[2] Sch Sci, Lab Mol Design & Drug Discovery, 639 Longmian Ave, Nanjing 211198, Jiangsu, Peoples R China

[3] China Pharmaceut Univ, State Key Lab Nat Med, 24 Tongjiaxiang, Nanjing 210009, Jiangsu, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 12期

基金：

中国国家自然科学基金;

关键词：

Epigenetic; Protein-protein interactions; Bromodomain; HDAC; Antiproliferative activity; BROMODOMAIN; DISCOVERY;

D O I：

10.1016/j.bmcl.2016.04.034

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The bromodomain protein module and histone deacetylase ( HDAC), which recognize and remove acetylated lysine, respectively, have emerged as important epigenetic therapeutic targets in cancer treatments. Herein we presented a novel design approach for cancer drug development by combination of bromodomain and HDAC inhibitory activity in one molecule. The designed compounds were synthesized which showed inhibitory activity against bromodomain 4 and HDAC1. The representative dual bromodomain/HDAC inhibitors, compound 11 and 12, showed potent antiproliferative activities against human leukaemia cell line K562 and MV4-11 in cellular assays. This work may lay the foundation for developing dual bromodomain/HDAC inhibitors as potential anticancer therapeutics. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：2931 / 2935

页数：5

共 50 条

[1] Synthesis and evaluation of novel dual BRD4/HDAC inhibitors
Amemiya, Seika
Yamaguchi, Takao
Hashimoto, Yuichi
Noguchi-Yachide, Tomomi
BIOORGANIC & MEDICINAL CHEMISTRY, 2017, 25 (14) : 3677 - 3684
[2] Discovery of selective HDAC/BRD4 dual inhibitors as epigenetic probes
Chen, Jingjing
Li, Yalei
Zhang, Jie
Zhang, Minmin
Wei, Aihuan
Liu, Hongchun
Xie, Zhicheng
Ren, Wenming
Duan, Wenwen
Zhang, Zhuo
Shen, Aijun
Hu, Youhong
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2021, 209
[3] Design, synthesis and biological evaluation of dihydroquinoxalinone derivatives as BRD4 inhibitors
Yang, Yifei
Zhao, Leilei
Xu, Bin
Yang, LingYun
Zhang, Jian
Zhang, Huibin
Zhou, Jinpei
BIOORGANIC CHEMISTRY, 2016, 68 : 236 - 244
[4] Design and synthesis of dual ALK/BRD4 inhibitors
Watts, Ellen
Tucker, Elizabeth
Heidenreich, David
Bellenie, Benjamin
Knapp, Stefan
Chesler, Louis
Hoelder, Swen
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2018, 255
[5] Design, synthesis and biological evaluation of novel indole derivatives as potential HDAC/BRD4 dual inhibitors and anti-leukemia agents
Cheng, Gaoliang
Wang, Zhi
Yang, Jinyu
Bao, Yu
Xu, Qihao
Zhao, Linxiang
Liu, Dan
BIOORGANIC CHEMISTRY, 2019, 84 : 410 - 417
[6] Dual HDAC/BRD4 inhibitors against cancer
Negar Omidkhah
Farzin Hadizadeh
Razieh Ghodsi
Medicinal Chemistry Research, 2021, 30 : 1822 - 1836
[7] Dual HDAC/BRD4 inhibitors against cancer
Omidkhah, Negar
Hadizadeh, Farzin
Ghodsi, Razieh
MEDICINAL CHEMISTRY RESEARCH, 2021, 30 (10) : 1822 - 1836
[8] Structure-based design, synthesis and in vitro antiproliferative effects studies of novel dual BRD4/HDAC inhibitors
Shao, Mingfeng
He, Linhong
Zheng, Li
Huang, Lingxiao
Zhou, Yuanyuan
Wang, Taijing
Chen, Yong
Shen, Mingsheng
Wang, Fang
Yang, Zhuang
Chen, Lijuan
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2017, 27 (17) : 4051 - 4055
[9] Design, Synthesis, and in vitro Biological Evaluation of 3,5-Dimethylisoxazole Derivatives as BRD4 Inhibitors
Li, Xiangyang
Zhang, Jian
Zhao, Leilei
Yang, Yifei
Zhang, Huibin
Zhou, Jinpei
CHEMMEDCHEM, 2018, 13 (13) : 1363 - 1368
[10] Design, synthesis, and biological evaluation of quinoxalinone derivatives as potent BRD4 inhibitors
Xu, Kai-Yan
Wang, Xue-Ting
Cheng, Lei
Cui, Qi-Hang
Shi, Jian-Tao
Zhang, Li-Wen
Chen, Shi-Wu
BIOORGANIC & MEDICINAL CHEMISTRY, 2023, 78

← 1 2 3 4 5 →