N-(2-金刚烷-1H-吲哚-5-基)取代苯甲酰胺合成及生物活性研究

Synthesis and biological activities of N-(2-adamantane-1H-indol-5-yl)substituted benzamide

以金刚烷甲酰氯为起始原料,亲核取代、环化、硝化和还原反应制得中间体2-金刚烷-5-氨基-1H-吲哚(5);再与取代酰氯反应,合成了5个N-(2-金刚烷-1H-吲哚-5-基)取代苯甲酰胺(6a—6e),其结构经1H NMR,13C NMR和HR-MS表征;采用四甲基偶氮唑盐(MTT)法研究了6a—6e对人肺癌细胞(A549)、人肝癌细胞(Hep G-2)和乳腺癌细胞(MCF-7)的体外抗肿瘤活性.结果显示:化合物6d体外抑制活性最优,其半数抑制浓度(IC50)分别为13. 45,11. 45,9. 56μmol/L.实验表明,化合物6d具有较好的抗肿瘤活性.

The intermediate 2-adamantane-5-amino-1 H-indole(5)was prepared from adamantine-substituted,cyclized,nitrated and reductive reactions using adamantyl chloride as starting material.Five N-(2-adamantane-1 H-indol-5-yl)-substituted benzamides(6a-6e)were synthesized by reaction with substituted acyl chlorides.Their structures were characterized by 1H NMR,13 C NMR and HR-MS.Tetramethyl azozolium salt(MTT)assay was used to study the in vitro antitumor activity of 6a-6e on human lung cancer cells(A549),human hepatoma cells(HepG-2)and breast cancer cells(MCF-7).The results showed that the optimal inhibitory activity in vitro reached at 6d,with half inhibition concentration(IC 50)of 13.45,11.45,9.56μmol/L respectively.