3-取代吲哚-2-酮类化合物的设计、合成及抗肿瘤活性研究

目的设计合成对微管蛋白和血管内皮细胞生长因子受体2(VEGFR-2)激酶具有双重抑制作用的3-取代吲哚-2-酮类化合物,考察其体外抑瘤活性。方法以取代的苯胺为起始原料,经缩合、环合、还原、取代等反应制得系列目标化合物,并考察该系列化合物对微管蛋白和肿瘤细胞的抑制活性。结果共合成了11个新的目标化合物。实验结果显示,化合物j9对微管蛋白和VEGFR-2激酶具有双重抑制活性。所有目标化合物对3种肿瘤细胞株均有中等强度的抑制活性。结论该类化合物是一类具有多靶点作用的抗肿瘤化合物。

Design, synthesis and anti-tumor activities in vitro of novel 3-substituted indolin-2-one compounds

Objective To compose and evaluate anti-tumor activities of 3-substituted indole-2-one compounds which may have dual inhibitory activities against both tubulin protein and VEGFR-2 tyrosine kinase. Methods Target compounds were prepared starting from substituted aniline via condensation, cyclization and reduction. Results 11 target compounds were synthesized and all the compounds displayed moderate anti-proliferative activities against three tumor cell lines. Compound j9 showed a certain inhibitory activity against both VEGFR-2 kinase and tubulin protein in vitro. Conclusion This series of indolin-2-one derivatives were found to be a novel kind of multi-target inhibitor.