一锅法合成新型吲哚-色胺酮类化合物  

One-pot synthesis of novel indole-tryptanthrin compounds

作　　者：叶文杰[1] 颜金武[1] 谭嘉恒[1] 古练权[1] 黄志纾[1] 

机构地区：[1]中山大学药学院,广东广州510080

出　　处：《中国药物化学杂志》2013年第5期363-367,共5页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(81001400);高等学校博士学科点专项科研基金项目(20110171110051)

摘　　要：目的合成新型结构的吲哚-色胺酮[6-(1H-吲哚-2-基)吲哚并[2,1-b]喹唑啉-12(5H)-酮]类化合物,并初步考察其代表性化合物3a的抗肿瘤活性。方法以2-吲哚酮为起始原料,经盐酸酸化后在过量三氯氧磷的条件下与相应的取代2-氨基苯甲酸经一锅法合成新的吲哚-色胺酮类化合物。采用MTT法考察化合物3a对不同肿瘤细胞的抑制作用。结果与结论合成了3个未见报道的新化合物,目标化合物的结构经质谱、核磁共振谱确证。活性测试结果表明,化合物3a对A549肿瘤细胞株显示出一定的抑制作用。目标化合物是在色胺酮结构中引入吲哚单元后形成的新骨架结构的化合物,将为进一步研究基于吲哚-色胺酮结构的先导化合物提供一个新的方向。Tryptanthrin is a naturally occurring alkaloid which possesses a broad spectrum of biological and pharmaceutical activities. Extensive efforts have been devoted to develop tryptanthrin derivatives as a new class of potential therapeutic agents. Herein, a facile and simple procedures described for the synthesis of novel indole-tryptanthrin （ 6-（ 1H-indol-2-yl ） indolo [ 2,1-b ] quinazolin-12 （5H） -one ） compounds. The new compounds 3a -3c were synthesized in mild conditions and no complicated purification was required. The structure of compound 3a was confirmed by LC-MS, 1H-NMR, 13 C.NMR, HMQC, HMBC, NOESY spectrum and HRMS. The plausible mechanism of the reaction was discussed and supported by theoretical analysis and experimental data. In addition, the cytotoxicity of compound 3a to different cell lines was tested using MTT method. The preliminary results showed that 3a displayed potent anticancer activity against A549 cancer cell line with the ICs0 around 41 ixmol.L-1. It may be a promising and valuable direction for developing novel lead compounds based on the structure of indole-tryptanthrin. To the best of our knowledge, there are very few reports about the extension of skeleton of tryptanthrin. This strategy on the synthesis of indole-tryptanthrin compounds will shed light on the further constructing of novel tryptanthrin skeleton.

关 键 词：2-吲哚酮 色胺酮 吲哚-色胺酮 一锅法 合成 

分 类 号：R914[医药卫生—药物化学]