State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Bioorg Med Chem. 2010 Jan 15;18(2):880-6. doi: 10.1016/j.bmc.2009.11.037. Epub 2009 Nov 22.
A series of amide-coupled benzoic nitrogen mustard derivatives as potential EGFR and HER-2 kinase inhibitors were synthesized and reported for the first time. Some of them exhibited significant EGFR and HER-2 inhibitory activity. Of all the studied compounds, compounds 5b and 5t exhibited the most potent inhibitory activity, which was comparable to the positive control erlotinib. Docking simulation was performed to position compounds 5b and 5t into the EGFR active site to determine the probable binding model. Antiproliferative assay results indicated that some of the benzoic nitrogen mustard derivatives possessed high antiproliferative activity against MCF-7. In particular, compounds 5b and 5t with potent inhibitory activity in tumor growth inhibition may function as potential antitumor agents.
一系列酰胺偶联的苯甲酸氮芥衍生物作为潜在的 EGFR 和 HER-2 激酶抑制剂被首次合成并报道。其中一些表现出显著的 EGFR 和 HER-2 抑制活性。在所研究的化合物中，化合物 5b 和 5t 表现出最强的抑制活性，与阳性对照药厄洛替尼相当。进行了对接模拟，将化合物 5b 和 5t 定位到 EGFR 的活性部位，以确定可能的结合模型。增殖抑制实验结果表明，一些苯甲酸氮芥衍生物对 MCF-7 具有高增殖抑制活性。特别是具有强肿瘤生长抑制抑制活性的化合物 5b 和 5t 可能作为潜在的抗肿瘤药物发挥作用。
