新型N-取代邻苯二甲酰亚胺-4-甲酰胺衍生物的合成及抗癌活性  

Synthesis and Anticancer Activities of Novel N-substituted Phthalmide-4-Formamide Derivatives

作　　者：何华龙 冯盏盏 高添桃 余洛汀[2] 奉强 HE Hua-long;FENG Zhan-zhan;GAO Tian-tao;YU Luo-ting;FENG Qiang(College of Chemical Engineering, Sichuan University, Chengdu 610041, China;State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China;School of Chemistry and Life Science, Chengdu Normal University, Chengdu 611130, China)

机构地区：[1]四川大学化学工程学院,四川成都610041 [2]四川大学生物治疗国家重点实验室,四川成都610041 [3]成都师范学院化学与生命科学学院,四川成都611130

出　　处：《合成化学》2020年第9期764-771,共8页Chinese Journal of Synthetic Chemistry

基　　金：四川省科技厅重点研发项目(2018SZ0007);四川省科技创新苗子工程项目(2018120)。

摘　　要：以1,2,3-苯三甲酸为原料,依次经分子内脱水、胺解反应和酰胺缩合3步反应合成了19个新型N-取代邻苯二甲酰亚胺-4-甲酰胺衍生物作为聚腺苷二磷酸核糖聚合酶1(PARP-1)抑制剂(4a^4s),其结构经1H NMR,13C NMR和HR-MS(ESI-TOF)表征。采用MTT法研究了4a^4s对胰腺癌细胞系Capan-1的体外抗癌活性,结果表明:对Capan-1的增值抑制活性最强的是4r(IC50=0.19μM),是模板化合物NMS-P118(IC50=2.20μM)的11倍。Nineteen novel N-substituted pthalmide-4-formamide drivatives were synthesized as poly(ADP-ribose)polymerase-1(PARP-1)inhibitors(4a^4s)by intramolecular dehydration,ammonolysis reaction and amidation using 1,2,3-benzenetricarboxylic acid as starting materials.The structures were characterized by 1H NMR,13C NMR and HR-MS(ESI-TOF).In vitro anticancer activities against pancreatic cancer cell line Capan-1,have been demonstrated by MTT assays.The results showed that the strongest inhibitory activity against Capan-1 cell line was compound 4r(IC50=0.19μM),11 times higher than template compound NMS-P118(IC50=2.20μM).

关 键 词：1 2 3-苯三甲酸 PARP-1抑制剂 邻苯二甲酰亚胺母核 抗癌活性 合成 

分 类 号：O621.3[理学—有机化学] O625[理学—化学]