Design, synthesis and antitumor evaluation of a new series of N-substituted-thiourea derivatives.
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.
Li
Jian
J
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.
Tan
Jin-zhi
JZ
Chen
Li-li
LL
Zhang
Jian
J
Shen
Xu
X
Mei
Chang-lin
CL
Fu
Li-li
LL
Lin
Li-ping
LP
Ding
Jian
J
Xiong
Bing
B
Xiong
Xi-shan
XS
Liu
Hong
H
Luo
Xiao-min
XM
Jiang
Hua-liang
HL
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
D000970:Antineoplastic Agents; D011505:Protein-Tyrosine Kinases; D013890:Thiourea