Journal
BIOORGANIC CHEMISTRY
Volume 86, Issue -, Pages 375-385Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2019.01.023
Keywords
Chalcone-dithiocarbamate; Catalase; DNA damage; Apoptosis; Epithelial-mesenchymal transition
Funding
- National Natural Sciences Foundations of China [81703541, 81673322]
- China Postdoctoral Science Foundation
- MEDCHEMEXPRESS
- MCE
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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.
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