Cao Xin, You Qi-Dong, Li Zhi-Yu, Liu Xiao-Rong, Xu Dan, Guo Qing-Long, Shang Jing, Chern Ji-Wang, Chen Meng-Ling
Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
Bioorg Med Chem Lett. 2008 Dec 1;18(23):6206-9. doi: 10.1016/j.bmcl.2008.10.006. Epub 2008 Oct 5.
Because both c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heterocycle amine-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, synthesized and evaluated as multiple targets agents in cancer therapy. All compounds were evaluated by two related enzyme inhibition assays and an anti-proliferation assay in vitro. The results showed that most compounds inhibited c-Src and iNOS well. The best compound 8 inhibited both enzymes with the IC(50) values of 34.8 nM and 26.7 microM. Several compounds also showed moderate anti-proliferation at 10 microM against colon and liver cancer cell lines.
由于c-Src和诱导型一氧化氮合酶（iNOS）都是肿瘤发生过程中的关键调节酶，因此设计、合成了一系列新型的4-杂环胺-3-喹啉甲腈作为这两种酶的有效双重抑制剂，并将其评估为癌症治疗中的多靶点药物。所有化合物均通过两种相关的酶抑制试验和体外抗增殖试验进行评估。结果表明，大多数化合物对c-Src和iNOS具有良好的抑制作用。最佳化合物8对这两种酶的抑制作用的半数抑制浓度（IC50）值分别为34.8 nM和26.7 μM。几种化合物在10 μM浓度下对结肠癌细胞系和肝癌细胞系也显示出中等程度的抗增殖作用。
