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Design and synthesis of formononetin-dithiocarbamate hybrids that inhibit growth and migration of PC-3 cells via MAPK/Wnt signaling pathways.

  • Author(s): 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
  • Zhang, Yan-Bing
  • et al.
Creative Commons Attribution 4.0 International Public License
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.

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