title: Aromatic diacylhydrazine derivatives as a new class of polo-like kinase 1 (PLK1) inhibitors.
abstract: A novel class of aromatic diacylhydrazine derivatives was designed as PLK1 inhibitors. All the 19 new synthesized compounds were assayed for antitumor activity against the respective cervical cancer cells. In which, nine compounds with better antitumor activities were further tested for their PLK1 inhibitory activity. Last, we have successfully found that compound 7k showed both the promising antitumor activity with IC50 of 0.17 μM against the cervical cancer cells, and also processed the most potent PLK1 inhibitory activity with IC50 of 0.03 μM. In addition, docking simulation also carried out in this study to give a potent prediction binding mode between the small molecule and PKL1 (PDB code: 1umw) protein.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: Lv
authors.affiliation: School of Life Sciences, Shandong University of Technology, Shandong 255049, People's Republic of China.
authors.forename: Feng-Jiao
authors.initials: FJ
authors.lastname: Guo
authors.affiliation: School of Life Sciences, Shandong University of Technology, Shandong 255049, People's Republic of China.
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Shandong University of Technology, Shandong 255049, People's Republic of China.
authors.lastname: Xiao-Han
authors.affiliation: School of Life Sciences, Shandong University of Technology, Shandong 255049, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Gui-Hua
authors.initials: GH
authors.lastname: Sheng
authors.affiliation: School of Life Sciences, Shandong University of Technology, Shandong 255049, People's Republic of China.
authors.forename: Shao-Song
authors.initials: SS
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China; School of Life Sciences, Shandong University of Technology, Shandong 255049, People's Republic of China. Electronic address: zhuhl@nju.edu.cn.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000097869:Polo-Like Kinase 1
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D006834:Hydrazines; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1
keywords: Aromatic diacylhydrazine; Computer simulation; Polo-like kinase 1