Design, synthesis and biological evaluation of coumarin-based N-hydroxycinnamamide derivatives as novel histone deacetylase inhibitors with anticancer activities

被引：26

作者：

Ding, Jiaoli ^{[1
]}

Liu, Jing ^{[2
]}

Zhang, Zhipeng ^{[1
]}

Guo, Jie ^{[1
]}

Cheng, Maojun ^{[1
]}

Wan, Yang ^{[1
]}

Wang, Rikang ^{[1
]}

Fang, Yuanying ^{[1
]}

Guan, Zhiyu ^{[2
]}

Jin, Yi ^{[1
]}

Xie, Sai-Sai ^{[1
]}

机构：

[1] Jiangxi Univ Tradit Chinese Med, Natl Pharmaceut Engn Ctr Solid Preparat Chinese H, Nanchang 330006, Jiangxi, Peoples R China

[2] Jiangxi Univ Tradit Chinese Med, Sch Pharm, Nanchang 330006, Jiangxi, Peoples R China

来源：

BIOORGANIC CHEMISTRY | 2020年 / 101卷

基金：

中国国家自然科学基金;

关键词：

Histone deacetylase; Coumarin; N-hydroxycinnamamide; Antiproliferative activity; Inhibitors; HDAC INHIBITORS; IN-VITRO; CELL-DEATH; APOPTOSIS; AGENTS;

D O I：

10.1016/j.bioorg.2020.104023

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：

A series of novel coumarin-based N-hydroxycinnamamide derivatives were designed and synthesized as histone deacetylase (HDAC) inhibitors. Most of the synthesized compounds showed potent HDAC inhibitory activity and significant antiproliferative activity against human cancer cell lines MCF-7, HepG2, HeLa and HCT-116. Among them, compound 14f displayed the most potent HDAC inhibition, especially against HDAC1 with IC50 value of 0.19 mu M, which was better than that of SAHA (IC50 = 0.23 mu M). It also showed the strongest antiproliferative activity towards HeLa cells and more than 26-fold selectivity for HDAC1 compared with HDAC6. Molecular docking studies revealed the possible binding modes of compound 14f into the two isoforms and provided a reasonable explanation for the selectivity. In addition, compound 14f could inhibit colony formation, upregulate the acetylation level of histone H3, and induce apoptosis and cell cycle arrest at G2/M phase in HeLa cells. Taken together, these results highlighted that compound 14f might be a promising HDAC inhibitor for cancer therapy.

引用

页数：14

共 43 条

[11]

Giannini G, 2012, FUTURE MED CHEM, V4, P1439, DOI [10.4155/FMC.12.80, 10.4155/fmc.12.80]

[12] Acetylation and deacetylation of non-histone proteins [J].

Glozak, MA ;

Sengupta, N ;

Zhang, XH ;

Seto, E .

GENE, 2005, 363 :15-23

[13] Molecular evolution of the histone deacetylase family: Functional implications of phylogenetic analysis [J].

Gregoretti, IV ;

Lee, YM ;

Goodson, HV .

JOURNAL OF MOLECULAR BIOLOGY, 2004, 338 (01) :17-31

[14] Coumarin-dithiocarbamate hybrids as novel multitarget AChE and MAO-B inhibitors against Alzheimer's disease: Design, synthesis and biological evaluation [J].

He, Qi ;

Liu, Jing ;

Lan, Jin-Shuai ;

Ding, Jiaoli ;

Sun, Yongbing ;

Fang, Yuanying ;

Jiang, Neng ;

Yang, Zunhua ;

Sun, Liyuan ;

Jin, Yi ;

Xie, Sai-Sai .

BIOORGANIC CHEMISTRY, 2018, 81 :512-528

[15] Small molecule HDAC inhibitors: Promising agents for breast cancer treatment [J].

Huang, Meiling ;

Zhang, Jian ;

Yan, Changjiao ;

Li, Xiaohui ;

Zhang, Juliang ;

Ling, Rui .

BIOORGANIC CHEMISTRY, 2019, 91

[16] Synthesis and biological evaluation of isoprenylated coumarins as potential anti-pancreatic cancer agents [J].

Jun, Maria ;

Bacay, Alyssa F. ;

Moyer, James ;

Webb, Andrew ;

Carrico-Moniz, Dora .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2014, 24 (19) :4654-4658

[17] Studies on coumarins and coumarin-related compounds to determine their therapeutic role in the treatment of cancer [J].

Lacy, A ;

O'Kennedy, R .

CURRENT PHARMACEUTICAL DESIGN, 2004, 10 (30) :3797-3811

[18] Post-Translational Modification of Human Histone by Wide Tolerance of Acetylation [J].

Li, Cuiling ;

Choi, Han-Pil ;

Wang, Xiaoyue ;

wu, Fei ;

Chen, Xinjun ;

Lu, Xin ;

Jing, Ruirui ;

Ryu, Hoon ;

Wang, Xingyuan ;

Azadzoi, Kazem M. ;

Yang, Jing-Hua .

CELLS, 2017, 6 (04)

[19] Development of 3-hydroxycinnamamide-based HDAC inhibitors with potent in vitro and in vivo anti-tumor activity [J].

Li, Xiaoyang ;

Hou, Jinning ;

Li, Xiaoguang ;

Jiang, Yuqi ;

Liu, Xueliang ;

Mu, Weiwei ;

Jin, Yiming ;

Zhang, Yingjie ;

Xu, Wenfang .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2015, 89 :628-637

[20] New tranylcypromine derivatives containing sulfonamide motif as potent LSD1 inhibitors to target acute myeloid leukemia: Design, synthesis and biological evaluation [J].

Liang, Liyun ;

Wang, Haiwen ;

Du, Yongliang ;

Luo, Bingling ;

Meng, Ning ;

Cen, Meifeng ;

Huang, Peng ;

Ganesan, A. ;

Wen, Shijun .

BIOORGANIC CHEMISTRY, 2020, 99

← 1 2 3 4 5 →