Marchand Pascal, Antoine Maud, Le Baut Guillaume, Czech Michael, Baasner Silke, Günther Eckhard
Nantes Université, Nantes Atlantique Universités, Département de Pharmacochimie, IICiMed UPRES EA 1155, Faculté de Pharmacie, 1 rue Gaston Veil 44035 Nantes, France.
Bioorg Med Chem. 2009 Sep 15;17(18):6715-27. doi: 10.1016/j.bmc.2009.07.048. Epub 2009 Jul 25.
The synthesis and study of the structure-activity relationships of cytotoxic compounds based on N-pyridinyl or N-aryl-2-(1-benzylindol-3-yl)glyoxamide skeleton, represented by the lead structures D-24241 and D-24851, are described. The presence of N-(pyridin-4-yl) moiety was crucial for activity and 2-[1-(4-chloro-3-nitrobenzyl)-1H-indol-3-yl]-2-oxo-N-(pyridin-4-yl)acetamide (55), the most potent derivative, showed IC(50)=39 nM, 51 nM and 11 nM against HeLa/KB (human cervix carcinoma), L1210 (murine leukemia) and SKOV3 (human ovarian carcinoma) cell lines proliferation assay, respectively, as active as the lead compounds.
本文描述了基于先导结构D - 24241和D - 24851的、以N - 吡啶基或N - 芳基 - 2 - (1 - 苄基吲哚 - 3 - 基)乙二酰胺骨架为基础的细胞毒性化合物的合成及其构效关系研究。N - (吡啶 - 4 - 基)部分的存在对活性至关重要；最有效的衍生物2 - [1 - (4 - 氯 - 3 - 硝基苄基)-1H - 吲哚 - 3 - 基]-2 - 氧代 - N - (吡啶 - 4 - 基)乙酰胺(55)，在针对HeLa/KB(人宫颈癌)、L1210(小鼠白血病)和SKOV3(人卵巢癌)细胞系的增殖试验中，分别显示出IC(50)=39 nM、51 nM和11 nM，与先导化合物活性相当。
