3-去氮腺苷类似物的合成及抗肿瘤活性  

Synthesis and antitumor activity of 3-deazaadenine analogues

作　　者：刘连[1] 黄笑玲 孙平华[2] 郭嘉亮[1] 

机构地区：[1]佛山科学技术学院口腔医学院,广东佛山528000 [2]暨南大学药学院,广东广州510632

出　　处：《沈阳药科大学学报》2018年第2期92-97,共6页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金青年科学基金资助项目(81503031);广东省科技计划资助项目(2016A020226004);广东省中医药建设专项资金资助项目(34016006);佛山科学技术学院博士启动基金资助项目(gg040952)

摘　　要：目的探讨3-去氮腺苷类似物的抗肿瘤细胞增殖活性及初步的构效关系和作用机制。方法以2-氯甲基-4-甲氧基-3,5-二甲基吡啶为起始原料设计合成新型3-去氮腺苷类似物,考察化合物的体外肿瘤细胞增殖抑制作用。结果与结论合成了12个目标化合物及中间体,其结构经~1H-NMR,^(13)C-NMR和ESI-MS表征。体外抗肿瘤活性研究显示,活性最好的化合物7a和10a对A549细胞的体外抗肿瘤活性IC_(50)分别是9.23μmol·L^(-1)以及11.44μmol·L^(-1),说明了这两个3-去氮腺苷类似物与阳性对照相比具有更好的抗肿瘤细胞增殖活性。Objective To explore the multiplication inhibitory activities of the tumor cells, the preliminary structure-activity relationship and action mechanism of 3-deazaadenine analogues. Methods 3-Deazaadenine analogues were synthesized taking 2-chloromethyl-4-methoxy-3,5-dimethylpyridine as starting materials. The multiplication inhibitory activities of the tumor cells of the all compounds were tested. Results and Conclu- sions Twelve target compounds and intermediates were synthesized, and their structures were characterized by IH-NMR, 13C-NMR and ESI-MS. Compounds 7a and 10a exhibited antiproliferative activities against A549 cell line with ICso values of 9. 23 μmol·L^-1 and 11.44μmol·L^-1, respectively. The results show that these two 3-deazaadenine analogues have good antiproliferative acitivities compared with positive control.

关 键 词：3-去氮腺苷衍生物 A549细胞 抗肿瘤活性 合成 

分 类 号：R914[医药卫生—药物化学]