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

被引：33
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
收藏
页码：375 / 385
页数：11
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