新型氮杂蒽醌衍生物的设计、合成及抗肿瘤活性  

Design,Synthesis and Antitumor Activities of Novel Aza-anthraquinone Derivatives

作　　者：李君如[1] 王梦迪 刘珊珊[1] 张欢[1] 张有来[1] LI Jun-ru;WANG Meng-di;LIU Shan-shan;ZHANG Huan;ZHANG You-lai(College of Chemistry and Chemical Engineering,Tianjin University of Technology,Tianjin 300384,China)

机构地区：[1]天津理工大学化学化工学院,天津300384

出　　处：《合成化学》2018年第4期261-265,共5页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(21303120);天津市自然科学基金资助项目(16JCQNJC13700;13JCYBJC42100)

摘　　要：以氮杂蒽醌为母核结构,通过引入卤素和氨基侧链,设计并合成了4种新型的氮杂蒽醌衍生物(AQ-1~4)。其中,以异喹啉为起始原料,依次经氧化,脱水和傅克环酰化反应,制得6,9-取代苯并[g]异喹啉-5,10-蒽醌卤代衍生物(AQ-1和AQ-2);AQ-F与胺类化合物发生芳环亲核取代反应,合成了6,9-二取代苯并[g]异喹啉-5,10-蒽醌衍生物(AQ-3和AQ-4),其结构经1H NMR,13C NMR和HR-MS(ESI)表征。采用CCK-8法研究了AQ-1~4对人肺癌细胞(A549),人乳腺癌细胞(MCF-7)和人宫颈癌细胞(Hela)的体外抗肿瘤活性。结果表明:AQ-4的抑制活性最好,IC50分别为14.84μmol·L^(-1),10.36μmol·L^(-1)和10.55μmol·L^(-1)。Four novel aza-anthroquinone derivatives(AQ-1~4)were designed and synthesized using aza-anthraquinone as mother nucleus and introducing halogens and amino side chains.Among them,6,9-dihalogenbenzo[g]isoquinoline-5,10-dione(AQ-1 and AQ-2)were obtained from isoquinoline via oxidation,dehydration and Friedel-Crafts bis-cycloacylation.Then 6,9-diaminobenzo[g]isoquinoline-5,10-dione derivatives(AQ-3 and AQ-4)were synthesized by the aromatic nucleophilic substitution reaction of AQ-1 and AQ-2 with amine compounds.All the structures of AQ-1~4 were characterized by 1 H NMR,13 C NMR and HR-MS(ESI).The in vitro antitumor activities of AQ-1~4 against human lung cancer cells(A549),human breast cancer cells(MCF-7)and human cervical cancer cells(Hela)were investigated by CCK-8 method.The results indicated that AQ-4 showed best inhibition activities with IC 50 of 14.84μmol·L-1,10.36μmol·L-1 and 10.55μmol·L-1.

关 键 词：氮杂蒽醌 异喹啉 合成 抗肿瘤活性 

分 类 号：O621.3[理学—有机化学] O626.3[理学—化学]