Discovery of novel chalcone-dithiocarbamates as ROS-mediated apoptosis inducers by inhibiting catalase

被引：36

作者：

Fu, Dong-Jun ^{[1
,2
,3
,5
]}

Li, Jia-Huan ^{[2
,3
]}

Yang, Jia-Jia ^{[2
,3
]}

Li, Ping ^{[2
,3
]}

Zhang, Yan-Bing ^{[2
,3
]}

Liu, Simeng ^{[4
]}

Li, Zhong-Rui ^{[2
,3
]}

Zhang, Sai-Yang ^{[1
,2
,3
]}

机构：

[1] Zhengzhou Univ, Sch Basic Med Sci, Zhengzhou 450001, Henan, Peoples R China

[2] Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou 450001, Henan, Peoples R China

[3] Zhengzhou Univ, Collaborat Innovat Ctr New Drug Res & Safety Eval, Zhengzhou 450001, Henan, Peoples R China

[4] Zhengzhou Univ, Affiliated Hosp 5, Dept Gastroenterol, Zhengzhou 450052, Henan, Peoples R China

[5] Univ Calif Irvine, Dept Urol, Orange, CA 92868 USA

来源：

BIOORGANIC CHEMISTRY | 2019年 / 86卷

基金：

中国博士后科学基金;

关键词：

Chalcone-dithiocarbamate; Catalase; DNA damage; Apoptosis; Epithelial-mesenchymal transition; ANTIPROLIFERATIVE ACTIVITY; MESENCHYMAL TRANSITION; DESIGN; HYBRIDS; DERIVATIVES; COMPLEXES; CELLS; BEARING; BINDING;

D O I：

10.1016/j.bioorg.2019.01.023

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：

Novel chalcone-dithiocarbamate hybrids were designed, synthesized and evaluated for antiproliferative activity against selected cancer cell lines (MGC803, MCF7, and PC3). Among these analogues, (E)-2-oxo-2-((4-(3-(3,4,5-trimethoxyphenyl) acryloyl) phenyl) amino) ethyl-4-(2-hydroxyethyl) piperazine-1-carbodithioate (12d) showed the best inhibitory activity against PC3 cells (IC50 = 1.05 mu M). Cellular mechanism studies elucidated 12d could inhibit colony formation, arrest cell cycle at G2/M phase and induce DNA damage against PC3 cells. Compound 12d also induced mitochondrial apoptosis by caspase activation, MMP decrease, ROS production and catalase (CAT) inhibition. Importantly, 12d inhibited epithelial-mesenchymal transition (EMT) process by regulating EMT-related proteins (E-cadherin, N-cadherin, Vimentin, MMP2, MMP9). These results indicated that 12d is a promising lead compound and deserves further investigation for prevention and treatment of human prostate cancer.

引用

页码：375 / 385

页数：11

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