新型氮杂蒽醌衍生物的设计、合成及抗肿瘤活性

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14.84 μmol· L-1,10.36 μmol· L-1和10.55 μmol· 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]isoquino-line-5,10-dione derivatives(AQ-3 and AQ-4)were synthesized by the aromatic nucleophilic substitu-tion reaction of AQ-1 and AQ-2 with amine compounds.All the structures of AQ-1~4 were charac-terized by 1H NMR, 13C 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 IC50of 14.84 μmol· L-1,10.36 μmol· L-1and 10.55 μmol· L-1.