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

• Published in: Acta pharmacologica Sinica Vol. 27; no. 9; pp. 1259 - 1271
• Main Authors: Li, Jian, Tan, Jin-zhi, Chen, Li-li, Zhang, Jian, Shen, Xu, Mei, Chang-lin, Fu, Li-li, Lin, Li-ping, Ding, Jian, Xiong, Bing, Xiong, Xi-shan, Liu, Hong, Luo, Xiao-min, Jiang, Hua-liang
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.09.2006
• Subjects: Adenocarcinoma - pathology; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Drug Screening Assays, Antitumor; Humans; Lung Neoplasms - pathology; N-代-硫脲; Protein-Tyrosine Kinases - antagonists & inhibitors; Thiourea - analogs & derivatives; Thiourea - chemical synthesis; Thiourea - chemistry; Thiourea - pharmacology; 抗癌抗菌素; 派生物
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1111/j.1745-7254.2006.00437.x

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 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 SPAC 1. Results： Forty new compounds （1- 2, 3a-g, 4a-w, and 5a-1） were designed, synthesized and bioassayed. Six compounds （1, 3e, 41, 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. Conclusion： This study provides a promising new template with potential antitumor activity.