title: Design and synthesis of formononetin-dithiocarbamate hybrids that inhibit growth and migration of PC-3 cells via MAPK/Wnt signaling pathways.
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.
authors.affiliation: School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: Dong-Jun
authors.initials: DJ
authors.lastname: Fu
authors.affiliation: School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Song
authors.affiliation: School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: Ruo-Wang
authors.initials: RW
authors.lastname: Mao
authors.affiliation: School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: Ruo-Han
authors.initials: RH
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: Ying-Chao
authors.initials: YC
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Hou
authors.affiliation: School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: Jia-Huan
authors.initials: JH
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: Cheng-Yun
authors.initials: CY
authors.lastname: Jin
authors.affiliation: School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Pathology and Laboratory Medicine, University of California, Irvine, Orange, CA 92868, USA.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Zi
authors.affiliation: School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Liu
authors.affiliation: School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China. Electronic address: celeron16@163.com.
authors.forename: Sai-Yang
authors.initials: SY
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yan-Bing
authors.initials: YB
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D007529:Isoflavones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000737:chemistry*; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D007529:Isoflavones; D013859:Thiocarbamates; C007768:formononetin
keywords: Dithiocarbamate; Formononetin; Growth; Migration