State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
Bioorg Med Chem. 2012 May 1;20(9):2789-95. doi: 10.1016/j.bmc.2012.03.040. Epub 2012 Mar 24.
A series of 1,3,4-thiadiazol-2-amide derivatives (5a-5y) have been designed and synthesized, and their biological activities were also evaluated as potential antiproliferation and FAK inhibitors. Among all the compounds, 5h showed the most potent activity in vitro, which inhibited the growth of MCF-7 and B16-F10 cell lines with IC(50) values of 0.45 and 0.31 μM, respectively. Compound 5h also exhibited significant FAK inhibitory activity (IC(50)=5.32 μM). Docking simulation was performed to position compound 5h into the FAK structure active site to determine the probable binding model. The results of antiproliferative and Western-blot assay demonstrated that compound 5h possessed good antiproliferative activity. Therefore, compound 5h with potent FAK inhibitory activity may be a potential anticancer agent.
设计并合成了一系列 1,3,4-噻二唑-2-甲酰胺衍生物（5a-5y），评估了它们作为潜在的抗增殖和 FAK 抑制剂的生物活性。在所有化合物中，5h 在体外表现出最强的活性，对 MCF-7 和 B16-F10 细胞系的生长抑制作用的 IC50 值分别为 0.45 和 0.31 μM。化合物 5h 还表现出显著的 FAK 抑制活性（IC50=5.32 μM）。进行了对接模拟，将化合物 5h 定位到 FAK 结构的活性位点，以确定可能的结合模型。增殖抑制和 Western blot 测定的结果表明，化合物 5h 具有良好的增殖抑制活性。因此，具有强效 FAK 抑制活性的化合物 5h 可能是一种有潜力的抗癌药物。
