双-(1-杂环-β-咔啉)-3-烷氨基衍生物的合成与抗肿瘤活性（英文）  

Synthesis and Antitumor Activities of Novel Bivalent 1-Heterocyclic-β-carbolines Linked by Alkylamino Spacer

作　　者：郭亮[1,2] 谢建伟[1,2] 范文玺 陈伟 代斌[1,2] 马芹 Guo Lianga b Xie Jianweia(a. School of Chemistry and Chemical Engineering, Shihezi University, Shihezi 83200 b. Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi 832003 c. Xinjiang Huashidan Pharmaceutical Research Co., Ltd., Urumqi 830011)

机构地区：[1]石河子大学化学化工学院,石河子832003 [2]新疆兵团化工绿色过程重点实验室,石河子832003 [3]新疆华世丹药物研究有限责任公司,乌鲁木齐830011

出　　处：《有机化学》2017年第7期1741-1747,共7页Chinese Journal of Organic Chemistry

基　　金：Project supported by the Program for Outstanding Youth Science and Technology Innovation Talents Training in Xinjiang Uygur Autonomous Region(No.qn2015jc067)~~

摘　　要：为寻找高效、低毒的抗肿瘤候选化合物,以1-杂环取代-β-咔啉-3-羧酸乙酯为原料,合成了一系列的双-(1-杂环-β-咔啉)-3-烷氨基衍生物.所有目标化合物经~~1H NMR、^(13)C NMR和HRMS进行结构确证.以顺铂为阳性对照药,采用四甲基偶氮唑盐(MTT)法考察了目标化合物体外抗肿瘤(22RV1,SK-OV-3,MCF-7,BGC-823,A375和769-P等10株细胞)活性.结果显示化合物5a^5h与阳性对照药和单取代β-咔啉衍生物相比具有很好的抗肿瘤活性,其IC_(50)值均小于10μmol·L^(-1),特别是化合物5d对769-P的抑制活性达到0.8μmol·L^(-1),化合物5h对22RV1的抑制活性达到0.6μmol·L^(-1).In order to find novel antitumor candidate compounds with high efficiency and low toxicity, a series of 1-heterocyclic substituted bivalent β-carbolines with a spacer of four or five methylene units between the two 3-methylamino group were synthesized, and the chemical structures were characterized by 〈sup〉1H NMR, 13C NMR, and HRMS. The cytotoxic activities of all bivalent β-carbolines were evaluated in vitro against a panel of human tumor cell lines（22RV1, SK-OV-3, MCF-7, LLC, Eca-109, BGC-823, HT-29, Hep G-2, A375, and 769-P） and compared with the positive control cisplatin and monovalent β-carbolines. The results demonstrated that compounds 5a5h exhibited potent cytotoxic activities with IC50 values lower than 10 μmol·L-1. In particular, compounds 5d and 5h, both of which had a spacer of five methylene units, exhibited significant inhibitory activity against 769-P and 22RV1 with IC50 values of 0.8 μmol·L-1 and 0.6 μmol·L-1, respectively.

关 键 词：双β-咔啉 合成 抗肿瘤活性 构效关系 

分 类 号：O626[理学—有机化学] TQ460.1[理学—化学]