title: Discovery of phenylpiperazine derivatives as IGF-1R inhibitor with potent antiproliferative properties in vitro.
abstract: A series of phenylpiperazine derivatives (3a-3q) were designed and synthesized. In vitro assays indicated that several phenylpiperazine derivatives had excellent antiproliferative properties against four cancer cell lines including multidrug-resistant cancer cell lines, with IC50 values in the low micromolar range. The average IC50 of the most active compound 3b is 0.024μM to the MCF-7 cell line. In addition, the mechanism of action of these new analogues was investigated by molecular docking studies, insulin-like growth factor 1-receptor (IGF-1R) kinase assay and apoptosis induced assay. These studies confirmed that these new phenylpiperazine derivatives maintain their mechanisms of action by disrupting IGF-1R kinase.
authors: School of Life Sciences, Shandong University of Technology, Zibo 255049, Shandong Province, PR China.
authors: Feng-Jiao
authors: FJ
authors: Guo
authors: School of Life Sciences, Shandong University of Technology, Zibo 255049, Shandong Province, PR China.
authors: Juan
authors: J
authors: Sun
authors: School of Life Sciences, Shandong University of Technology, Zibo 255049, Shandong Province, PR China.
authors: Li-Li
authors: LL
authors: Gao
authors: School of Life Sciences, Shandong University of Technology, Zibo 255049, Shandong Province, PR China.
authors: Xin-Yi
authors: XY
authors: Wang
authors: School of Life Sciences, Shandong University of Technology, Zibo 255049, Shandong Province, PR China.
authors: Yang
authors: Y
authors: Zhang
authors: School of Life Sciences, Shandong University of Technology, Zibo 255049, Shandong Province, PR China.
authors: Shao-Song
authors: SS
authors: Qian
authors: School of Life Sciences, Shandong University of Technology, Zibo 255049, Shandong Province, PR China.
authors: Hai-Liang
authors: HL
authors: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D017526:Receptor, IGF Type 1; C031503:phenylpiperazine
keywords: Apoptosis; Computer simulation; IGF-1R inhibitors; Phenylpiperazine