胍基修饰的5-甲基-吲哚[2,3-b]喹啉衍生物的设计、合成及抗肿瘤活性筛选  

Design,synthesis and anti-proliferative evaluation of guanidyl modified 5-methyl-indolo[2,3-b]quinolines

作　　者：王力[1] 赵泽芳 韦思平 陈平 王钦[1] 杜曦[2] 

机构地区：[1]泸州医学院药物化学教研室,四川泸州646000 [2]泸州医学院化学教研室,四川泸州646000

出　　处：《化学研究与应用》2015年第7期1019-1023,共5页Chemical Research and Application

基　　金：四川省教育厅项目(13ZB0254)资助;泸州市科技局项目(2013-R-51(6/18);2013LZLY-K71;2013LZLY-K58)资助

摘　　要：以吲哚3-羧酸甲酯为起始原料,经偶联、环化和卤代合成中间体(3)。对化合物3进行11位氨基修饰,制备了中间体(4和6)。在1H-吡唑-1-甲脒盐酸盐的作用下,合成具有潜在抗肿瘤活性的目标产物11-位胍基修饰的5-甲基-吲哚[2,3-b]喹啉衍生物(5a,5b和7)。目标产物5a,5b和7经红外光谱、核磁氢谱、碳谱、高分辨质谱等方法对其结构进行了确认,并进行了抗肿瘤活性初筛。结果显示,该方法可以方便有效地制备含胍基的5-甲基吲哚[2,3-b]喹啉衍生物。目标产物皆具有抗癌细胞增生的作用,其中5a活性最强,对A549细胞的IC50值达到0.78±0.09μM,且对三种癌细胞株都具有最好的抑制活性。The design,synthesis and characterization of certain 11-aminoalkylamino-substituted 5-methyl-indolo[2,3-b]quinoline derivatives as potential anti-proliferative agent were reported. Indole 3-carboxylate was used as starting material. After coupling,cyclization and halogenation to form intermediate 3,the final product 5a,5b and 7 were achieved by modification of intermediate 3 at the 11-position,with an up to 73%yield in the guanidyl step. The structures of the final products 5a,5b and 7 were confirmed by IR,1H NMR,13 C NMR and HRMS spectral analysis. This method provided an efficient protocol to prepare guanidyl modified 5-methyl-indolo[2,3-b]quinolines derivatives. The anti-proliferative activity of the final products was evaluated in three cancer cell lines. The compound 5a was the most promising compound with an IC50 valued of 0. 78±0. 09μM against A549 cell line.

关 键 词：5-甲基-吲哚[2 3-b]喹啉 抗肿瘤试剂 生物碱 胍基衍生物 

分 类 号：O626[理学—有机化学]