State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
Bioorg Med Chem Lett. 2010 Jul 15;20(14):4163-7. doi: 10.1016/j.bmcl.2010.05.080. Epub 2010 May 24.
A series of novel 2-chloro-pyridine derivatives containing flavone, chrome or dihydropyrazole moieties as potential telomerase inhibitors were synthesized. The bioassay tests showed that compounds 6e and 6f exhibited some effect against gastric cancer cell SGC-7901 with IC(50) values of 22.28+/-6.26 and 18.45+/-2.79 microg/mL, respectively. All title compounds were assayed for telomerase inhibition by a modified TRAP assay, the results showed that compound 6e can strongly inhibit telomerase with IC(50) value of 0.8+/-0.07 microM. Docking simulation was performed to position compound 6e into the active site of telomerase (3DU6) to determine the probable binding model.
一系列新型的含黄酮、铬或二氢吡唑部分的 2-氯吡啶衍生物被合成出来，作为潜在的端粒酶抑制剂。生物测定试验表明，化合物 6e 和 6f 对胃癌细胞 SGC-7901 表现出一定的抑制作用，IC（50）值分别为 22.28+/-6.26 和 18.45+/-2.79 microg/mL。所有标题化合物都通过改良的 TRAP 测定法进行了端粒酶抑制试验，结果表明化合物 6e 可以强烈抑制端粒酶，IC（50）值为 0.8+/-0.07 microM。进行对接模拟，将化合物 6e 定位到端粒酶（3DU6）的活性部位，以确定可能的结合模型。
