Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, 205 Luo Shi Road, Wuhan, Hubei 430070, PR China.
Eur J Med Chem. 2013 Aug;66:531-9. doi: 10.1016/j.ejmech.2013.05.045. Epub 2013 Jun 6.
A series of pyrido[3,2-α]carbazole derivatives and their analogues have been prepared and evaluated for their antitumour activity against human lung cancer A549 cells and colon cancer HT29 cells. The intermediates 4a-4k are successfully synthesized from 1a-1k and ethyl 2-(3-bromopyridin-2-yl)acetate by Knoevenagel condensation and intramolecular Heck-type reaction, and this is a novel and efficient synthetic approach to the core scaffold of the target compounds. These target compounds have shown an interesting antitumour profile towards the tested cell lines with IC50 values ranging from 0.07 μM to 4.45 μM. Among all the compounds synthesized, 8 compounds show higher potency than R16, 12 compounds are as potent as R16, and 6 compounds are less potent than R16. The best compound 24 is 7 times and approximately 10 times as potent as R16 against A549 and HT29 cells, respectively.
已经制备了一系列吡啶并[3,2-α]咔唑衍生物及其类似物，并对它们对人肺癌 A549 细胞和结肠癌 HT29 细胞的抗肿瘤活性进行了评价。中间体 4a-4k 是由 1a-1k 和乙基 2-(3-溴吡啶-2-基)乙酸酯通过 Knoevenagel 缩合和分子内 Heck 型反应成功合成的，这是一种合成目标化合物核心支架的新颖而有效的方法。这些目标化合物对测试的细胞系表现出有趣的抗肿瘤特征，IC50 值范围为 0.07 μM 至 4.45 μM。在所合成的所有化合物中，有 8 个化合物的活性高于 R16，有 12 个化合物的活性与 R16 相当，有 6 个化合物的活性低于 R16。最佳化合物 24 对 A549 和 HT29 细胞的活性分别是 R16 的 7 倍和大约 10 倍。
