蓓萨罗汀衍生物的合成及其抗肿瘤活性研究  

Synthesis and evaluation of antitumor activities of bexarotene derivatives

作　　者：张玉娟[1] 苏专专[1] 王立辉[2] 郑洪丽[2] 杨静玉[2] 陈国良[1] 

机构地区：[1]沈阳药科大学基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳110016 [2]沈阳药科大学生命科学与生物制药学院药理系,辽宁沈阳110016

出　　处：《中国药物化学杂志》2014年第3期183-187,共5页Chinese Journal of Medicinal Chemistry

摘　　要：目的以抗肿瘤药蓓萨罗汀为先导化合物,设计新的蓓萨罗汀羟肟酸衍生物,并对其体外抗肿瘤活性进行初步评价。方法以1,1,4,4,6-五甲基-1,2,3,4-四氢化萘为起始原料,经过傅克反应、还原反应、缩合反应合成目标化合物;以HL-60细胞为测试肿瘤细胞株,采用台盼蓝法(MTT)测试目标化合物体外抗肿瘤活性。结果与结论合成了12个未见文献报道的蓓萨罗汀羟肟酸衍生物,其结构经ESI-MS、1H-NMR谱确认。体外测试结果显示,化合物7、9对HL-60细胞增殖有一定抑制作用,在抗肿瘤方面可能具有发展潜力。Tumors are serious harmful to human health and life. Novel more powerful antitumor agents are more urgent. It was reported that the antitumor activity of the compounds was significantly improved when retinoic acid compounds were combined with HDAC inhibitors. In this article, twelve derivatives of bexaro- tene were designed based on DW22 （a RXR/HADC dual-targeted anticancer agent）and prepared starting from 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene via Friedel-Crafts reaction, reduction reaction and condensation reaction. All target compounds have not been reported in the literatures, their structures were confirmed by ESI-MS and 1H-NMR. The in vitro antitumor activities were evaluated by the MTT assay on HL-60 human tumor cell lines. The result indicated that compounds 7 and 9 showed certain activities with IC50 values of 54.07 μmol· L- 1 and 38.26 μmol·L -1 to HL-60 human tumor cell lines.

关 键 词：蓓萨罗汀 羟肟酸类 抗肿瘤 MTT法 

分 类 号：R914[医药卫生—药物化学]