1. Design and synthesis of formononetin-dithiocarbamate hybrids that inhibit growth and migration of PC-3 cells via MAPK/Wnt signaling pathways.
- Author
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Fu, Dong-Jun, Zhang, Li, Song, Jian, Mao, Ruo-Wang, Zhao, Ruo-Han, Liu, Ying-Chao, Hou, Yu-Hui, Li, Jia-Huan, Yang, Jia-Jia, Jin, Cheng-Yun, Li, Ping, Zi, Xiao-Lin, Liu, Hong-Min, Zhang, Sai-Yang, and Zhang, Yan-Bing
- Subjects
Antineoplastic Agents: chemical synthesis ,chemistry ,pharmacology ,Apoptosis: drug effects ,Cell Line ,Tumor ,Cell Movement: drug effects ,Cell Proliferation: drug effects ,Chemistry Techniques ,Synthetic ,Dose-Response Relationship ,Drug ,Drug Design ,Drug Screening Assays ,Antitumor ,Drug Synergism ,G1 Phase Cell Cycle Checkpoints: drug effects ,Humans ,Isoflavones: chemical synthesis ,chemistry ,pharmacology ,MAP Kinase Signaling System: drug effects ,Structure-Activity Relationship ,Thiocarbamates: chemistry ,Wnt Signaling Pathway: drug effects - Abstract
A series of novel formononetin-dithiocarbamate derivatives were designed, synthesized and evaluated for antiproliferative activity against three selected cancer cell line (MGC-803, EC-109, PC-3). The first structure-activity relationship (SAR) for this formononetin-dithiocarbamate scaffold is explored in this report with evaluation of 14 variants of the structural class. Among these analogues, tert-butyl 4-(((3-((3-(4-methoxyphenyl)-4-oxo-4H-chromen-7-yl)oxy)propyl)thio)carbonothioyl)piperazine-1-carboxylate (8i) showed the best inhibitory activity against PC-3 cells (IC50 = 1.97 μM). Cellular mechanism studies elucidated 8i arrests cell cycle at G1 phase and regulates the expression of G1 checkpoint-related proteins in concentration-dependent manners. Furthermore, 8i could inhibit cell growth via MAPK signaling pathway and inhibit migration via Wnt pathway in PC-3 cells.
- Published
- 2017