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 DJ, Zhang L, Song J, Mao RW, Zhao RH, Liu YC, Hou YH, Li JH, Yang JJ, Jin CY, Li P, Zi XL, Liu HM, Zhang SY, and Zhang YB
- Subjects
- Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Apoptosis drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Chemistry Techniques, Synthetic, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Drug Synergism, G1 Phase Cell Cycle Checkpoints drug effects, Humans, Isoflavones chemical synthesis, Structure-Activity Relationship, Cell Movement drug effects, Drug Design, Isoflavones chemistry, Isoflavones pharmacology, MAP Kinase Signaling System drug effects, 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 (IC
50 = 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., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)- Published
- 2017
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