Design, synthesis and antitumor evaluation of a new series of N-substituted-thiourea derivatives
Design, synthesis and antitumor evaluation of a new series of N-substituted-thiourea derivatives
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DOI：
10.1111/j.1745-7254.2006.00437.x
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发表时间：
2006-09-01
影响因子：
8.2
通讯作者：
Jiang, Hua-liang
中科院分区：
文献类型：
--
作者：
Li, Jian;Tan, Jin-zhi;Jiang, Hua-liang
目的：设计并合成一类具有N-（2-氧-1,2-二氢喹啉-3-酰基甲基）-硫脲结构的新型蛋白酪氨酸激酶抑制剂。方法：首先，利用虚拟筛选方法结合基于表面等离子体共振的结合试验对化合物1和2进行鉴定。随后，选取化合物1和2的3个区域进行化学修饰。所有化合物对人肺腺癌细胞株SPAC1均有较强的抑制活性。结果：设计、合成了40个新化合物（1-2、3a-g、4a-w和5a-1）并进行了生物测定。6个化合物（1,3e, 41,4w， 5a和5b）对SPAC1肿瘤细胞系表现出良好的抑制活性。化合物5a的抑制活性比原化合物1提高约10倍。结论：该研究提供了一种具有潜在抗肿瘤活性的新模板。
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 SPAC1. 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.