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

[41] Discovery of 4,5-dihydro-benzo[g]indazole-based hydroxamic acids as HDAC3/BRD4 dual inhibitors and anti-tumor agents
Li, Bo
Chen, Yibing
Wang, Siyuan
Jin, Bo
Yang, Jinyu
Niu, Qun
Hao, Guizhou
Wang, Ning
Zhang, Wenchao
Zhao, Linxiang
Wen, Jiachen
Liu, Dan
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2025, 285
[42] Design, synthesis and biological evaluation of pyrimidine base hydroxamic acid derivatives as dual JMJD3 and HDAC inhibitors
Li, Anqi
Zheng, Wenwen
Xiao, Boren
Huang, Wenjun
Li, Lulu
Luo, Minglang
Liu, Zijian
Chu, Bizhu
Jiang, Yuyang
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2023, 94
[43] Design, synthesis, and in vitro evaluation of epigoitrin derivatives as neuraminidase inhibitors
Meng, Fanli
Yin, Yan
Lu, Cheng
Duan, Yongbin
Zhu, Yaohua
Huang, Chen
Zhou, Yiming
Xu, Xu
Wu, Fanhong
MONATSHEFTE FUR CHEMIE, 2018, 149 (11): : 2037 - 2046
[44] Development and Evaluation of [11C]I-58: A Novel PET Radiotracer Targeting BRD4 BD2 for Advanced Epigenetic Imaging
Wang, Yanli
Wang, Yongle
Xu, Yulong
Tocci, Darcy
Wang, Changning
ACS OMEGA, 2024, 9 (34): : 36177 - 36184
[45] Design, synthesis, and evaluation of biphenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors
Dallavalle, Sabrina
Cincinelli, Raffaella
Nannei, Raffaella
Merlini, Lucio
Morini, Gabriella
Penco, Sergio
Pisano, Claudio
Vesci, Loredana
Barbarino, Marcella
Zuco, Valentina
De Cesare, Michelandrea
Zunino, Franco
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2009, 44 (05) : 1900 - 1912
[46] Design, synthesis and biological evaluation of novel c-Met/HDAC dual inhibitors
Dong, Yuhong
Hu, Hao
Sun, Yuwei
Qin, Mingze
Gong, Ping
Hou, Yunlei
Zhao, Yanfang
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2020, 30 (23)
[47] Design and Synthesis of sEH/HDAC6 Dual-Targeting Inhibitors for the Treatment of Inflammatory Pain
Xu, Huashen
Chen, Yuanguang
Tong, Hua
Chen, Lu
Morisseau, Christophe
Zhou, Zijian
Zhuang, Junning
Song, Chuqiao
Cai, Pengcheng
Liu, Zhongbo
Hammock, Bruce D.
Chen, Guoliang
JOURNAL OF MEDICINAL CHEMISTRY, 2024, 67 (15) : 12887 - 12911
[48] Novel 4-Acrylamido-Quinoline Derivatives as Potent PI3K/mTOR Dual Inhibitors: The Design, Synthesis, and in vitro and in vivo Biological Evaluation
Ma, Xiaodong
Shen, Li
Zhang, Jiankang
Liu, Guoqiang
Zhan, Shuyu
Ding, Baoyue
Lv, Xiaoqing
FRONTIERS IN CHEMISTRY, 2019, 7
[49] Design, synthesis, and evaluation of 4-(3-(3,5-dimethylisoxazol-4-yl)benzyl)phthalazin-1(2H)-one derivatives: potent BRD4 inhibitors with anti-breast cancer activity
Li, Yingpeng
Chu, Xinhong
Yin, Yu
Li, Hongkun
Fu, Hui
Feng, Xinchi
Deng, Yanru
Ge, Jun
FRONTIERS IN PHARMACOLOGY, 2023, 14
[50] Design, synthesis, and evaluation of isoindolinone-hydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors
Lee, Shoukou
Shinji, Chihiro
Ogura, Kiyoshi
Shimizu, Motomu
Maeda, Satoko
Sato, Mayumi
Yoshida, Minoru
Hashimotoa, Yuichi
Miyachi, Hiroyuki
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (17) : 4895 - 4900

← 1 2 3 4 5 →