State Key Laboratory of Pollution Control and Resource Reuse, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
Bioorg Med Chem. 2010 Jan 1;18(1):314-9. doi: 10.1016/j.bmc.2009.10.051. Epub 2009 Oct 30.
Two series of thiazolidinone derivatives designing for potential EGFR and HER-2 kinase inhibitors have been discovered. Some of them exhibited significant EGFR and HER-2 inhibitory activity. Compound 2-(2-(5-bromo-2-hydroxybenzylidene)hydrazinyl)thiazol-4(5H)-one (12) displayed the most potent inhibitory activity (IC(50)=0.09 microM for EGFR and IC(50)=0.42 microM for HER-2), comparable to the positive control erlotinib. Docking simulation was performed to position compound 12 into the EGFR active site to determine the probable binding model. Antiproliferative assay results indicating that some of the thiazolidinone derivatives own high antiproliferative activity against MCF-7. Compound 12 with potent inhibitory activity in tumor growth inhibition would be a potential anticancer agent.
已经发现了两个噻唑烷酮衍生物系列，它们被设计为潜在的 EGFR 和 HER-2 激酶抑制剂。其中一些表现出显著的 EGFR 和 HER-2 抑制活性。化合物 2-(2-(5-溴-2-羟基苯亚甲基)腙基)噻唑-4(5H)-酮（12）显示出最强的抑制活性（对 EGFR 的 IC50=0.09 μM，对 HER-2 的 IC50=0.42 μM），可与阳性对照药厄洛替尼相媲美。进行了对接模拟，将化合物 12 定位到 EGFR 的活性部位，以确定可能的结合模型。增殖抑制试验结果表明，一些噻唑烷酮衍生物对 MCF-7 具有高增殖抑制活性。具有肿瘤生长抑制活性的化合物 12 可能是一种潜在的抗癌药物。
