1-(5-取代糠基)吲哚啉-2-酮衍生物的合成和初步抗肿瘤活性

为了寻找具有较好抗肿瘤活性的新型吲哚啉-2-酮类化合物，本研究以5-甲酰基-2,4-二甲基-1H-吡咯-3-羧酸乙酯与5位不同取代的吲哚啉-2-酮(2a～2d)为原料，首先经缩合得3-吡咯亚甲基-吲哚啉-2-酮(3a～3d)，再经N烃化反应得到1-(5-甲酰基糠基)-3-(吡咯亚甲基)-吲哚啉-2-酮(4a～4d)，然后与吲哚啉-2-酮缩合得到以5-亚甲基糠基连接的双吲哚啉-2-酮化合物(5a～5d)。所合成的12个新型吲哚啉-2-酮类化合物的结构经核磁共振谱、质谱和元素分析确认。采用四氮唑盐(MTT)还原法测试所合成化合物的体外抗肿瘤活性，结果表明所合成的化合物均有一定的抗肿瘤作用，其中6个化合物对SPC-A1肺癌肿瘤株体外抑制活性优于舒尼替尼，特别是化合物5a～5d， IC₅₀值均小于5 μmol·L^-1，值得作为抗肿瘤药物先导化合物。

Synthesis of 1-furfuryl-indolin-2-one derivatives and preliminary evaluation of their antitumor activities

In order to find new indolin-2-one derivatives as antitumor agents, a series of 3-pyrrole substituted 1-(5-formyl-2-furanylmethyl) indolin-2-one derivatives were designed and synthesized. 5-Formyl-2 ,4-dimethyl-lH-pyrrole-3-carboxylic acid ethyl ester was condensed with 5-substituted indolin-2-one 2a-2d to afford 3-(pyrrol-2-yl) -methylidenyl] indolin-2-ones 3a-3d. Through N-alkylation, 1-(5-formyl-furfuryl) -indolin-2-one 4a-4d were prepared. Compounds 4a-4d were then condensed with indolin-2-one to afford bis-indolin-2-one derivatives 5a-5d. The structures of the synthesized compounds were determined by 1H NMR, MS and element analysis. Antitumor activities of all the synthesized compounds in vitro were tested. All the 12 synthesized compounds possess antitumor activities against SPC-A1 strain. Especially the compounds 5a-5d possess potent antitumor activities better than sunitinib. Their IC50 are all below 5 micromol x L(-1).