title: Design, synthesis and antitumor evaluation of a new series of N-substituted-thiourea derivatives.
abstract: OBJECTIVE
  To design and synthesize a novel class of protein tyrosine kinase inhibitors, featuring the N-(2-oxo-1,2-dihydroquinolin-3-yl-methyl)-thiourea framework.
  
  
  METHODS
  First, compounds 1 and 2 were identified using the virtual screening approach in conjunction with binding assay based on surface plasmon resonance. Subsequently, 3 regions of compounds 1 and 2 were selected for chemical modification. All compounds were characterized potent inhibitory activities toward the human lung adenocarcinoma cell line SPAC1.
  
  
  RESULTS
  Forty new compounds (1-2, 3a-g, 4a-w, and 5a-l) were designed, synthesized and bioassayed. Six compounds (1, 3e, 4l, 4w, 5a, and 5b) were found to show promising inhibitory activity against the SPAC1 tumor cell line. The inhibitory activity of compound 5a increases approximately 10 times more than that of the original compound 1.
  
  
  CONCLUSIONS
  This study provides a promising new template with potential antitumor activity.
authors.affiliation: Drug Discovery and Design Centre, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Jin-zhi
authors.initials: JZ
authors.lastname: Tan
authors.forename: Li-li
authors.initials: LL
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Xu
authors.initials: X
authors.lastname: Shen
authors.forename: Chang-lin
authors.initials: CL
authors.lastname: Mei
authors.forename: Li-li
authors.initials: LL
authors.lastname: Fu
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Lin
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.forename: Bing
authors.initials: B
authors.lastname: Xiong
authors.forename: Xi-shan
authors.initials: XS
authors.lastname: Xiong
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Xiao-min
authors.initials: XM
authors.lastname: Luo
authors.forename: Hua-liang
authors.initials: HL
authors.lastname: Jiang
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D011505:Protein-Tyrosine Kinases; D013890:Thiourea