Design,synthesis and antitumor evaluation of a new series of N-substi-tuted-thiourea derivatives

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:jerryymy
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Aim: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 screeningapproach in conjunction with binding assay based on surface plasmon resonance.Subsequently,3 regions of compounds 1 and 2 were selected for chemical modifica-tion.All compounds were characterized potent inhibitory activities toward thehuman lung adenocarcinoma cell line SPAC 1.Results:Forty new compounds(1-2,3a-g,4a-w,and 5a-l)were designed,synthesized and bioassayed.Six com-pounds(1,3e,41,4w,5a,and 5b)were found to show promising inhibitory activityagainst the SPAC1 tumor cell line.The inhibitory activity of compound 5aincreases approximately 10 times more than that of the original compound 1.Conclusion:This study provides a promising new template with potential antitu-mot activity. Aim: 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 using the virtual screening assay in conjunction with binding assay based on surface plasmon resonance. Substituted, 3 regions of compounds 1 and 2 were selected for chemical modifica- tion. All compounds were potent inhibitory activities toward the human lung adenocarcinoma cell line SPAC 1. Results: Forty new compounds (1-2,3a-g, 4a-w, and 5a-l) were designed, synthesized and bioassayed. Sim com pounds (1,3e, 41,4w, 5a, and 5b) were found to show promising inhibitory activity of the SPAC1 tumor cell line. The inhibitory activity of compound 5aincreases approximately 10 times more than that of the original compound 1. Conlusion: This study provides a promising new template with potential antitu-mot activity.
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