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

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

  • Eur J Med Chem. 2017 Feb 15:127:87-99. doi: 10.1016/j.ejmech.2016.12.027.
Dong-Jun Fu 1,  Li Zhang 1,  Jian Song 1,  Ruo-Wang Mao 1,  Ruo-Han Zhao 1,  Ying-Chao Liu 1,  Yu-Hui Hou 1,  Jia-Huan Li 1,  Jia-Jia Yang 1,  Cheng-Yun Jin 1,  Ping Li 1,  Xiao-Lin Zi 2,  Hong-Min Liu 1,  Sai-Yang Zhang 3,  Yan-Bing Zhang 4
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China.
  • 2 Pathology and Laboratory Medicine, University of California, Irvine, Orange, CA 92868, USA.
  • 3 School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China. Electronic address: celeron16@163.com.
  • 4 School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China. Electronic address: zhangyb@zzu.edu.cn.
PMID: 28038329 DOI: 10.1016/j.ejmech.2016.12.027
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.

Keywords

Dithiocarbamate; Formononetin; Growth; Migration.

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