State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Bioorg Med Chem Lett. 2011 Oct 15;21(20):6116-21. doi: 10.1016/j.bmcl.2011.08.039. Epub 2011 Aug 16.
A series of 1,3,4-thiadiazole derivatives containing 1,4-benzodioxan (2a-2s) have been synthesized to screen for FAK inhibitory activity. Compound 2p showed the most potent biological activity against HEPG2 cancer cell line (EC(50)=10.28 μg/mL for HEPG2 and EC(50)=10.79 μM for FAK), which was comparable to the positive control. Docking simulation was performed to position compound 2p into the FAK structure active site to determine the probable binding model. The results of antiproliferative and Western-blot assay demonstrated that compound 2p possessed good antiproliferative activity against HEPG2 cancer cell line. Therefore, compound 2p with potent FAK inhibitory activity may be a potential anticancer agent against HEPG2 cancer cell.
已经合成了一系列含有 1,4-苯并二恶烷的 1,3,4-噻二唑衍生物（2a-2s），以筛选 FAK 抑制活性。化合物 2p 对 HEPG2 癌细胞系表现出最强的生物活性（EC（50）=10.28μg/mL 用于 HEPG2 和 EC（50）=10.79μM 用于 FAK），与阳性对照相当。进行了对接模拟，将化合物 2p 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 分析的结果表明，化合物 2p 对 HEPG2 癌细胞系具有良好的增殖抑制活性。因此，具有强大 FAK 抑制活性的化合物 2p 可能是一种针对 HEPG2 癌细胞的潜在抗癌药物。
