新型法尼基硫代水杨酸/羟基肉桂酸偶联物的合成及其抗肿瘤活性  

Synthesis and biological evaluation of novel farnesylthiosalicylic acid /hydroxylcinnamic acid hybrids as potential antitumor agents

作　　者：王志强[1,2] 王雪敏[2] 张伟[2] 王新杨[2] 凌勇[2,3] 陈莉[1] 

机构地区：[1]中国药科大学天然药物化学教研室,南京210009 [2]南通大学药学院,南通226001 [3]中国药科大学天然药物活性组分与药效国家重点实验室,南京210009

出　　处：《中国药科大学学报》2014年第4期392-399,共8页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.81302628);江苏省自然科学基金资助项目(No.BK2011389);南通市应用研究资助项目(No.BK2012085)~~

摘　　要：通过偶联法尼基硫代水杨酸(FTS)的羧基与羟基肉桂酸的酚羟基,设计合成了16个新型FTS/羟基肉桂酸偶联物(7a^7p),并对其进行了体外抗肿瘤活性研究。结果表明,大部分化合物对6种人肿瘤细胞具有较强的抗增殖活性,其中,化合物7b表现出最佳的肿瘤细胞增殖抑制活性,对所测肿瘤细胞的IC50为5.51~9.25μmol/L,优于FTS和索拉非尼的活性。并且,化合物7b可以选择性地抑制肿瘤细胞的生长,而对正常细胞损伤较小。此外,流式细胞分析显示化合物7b可以浓度依赖性地诱导SMMC-7721细胞凋亡。Novel hybrid compounds 7a-Tp were designed and synthesized via conjugating farnesylthiosalicylic acid（ITS） and hydroxylcinnamic acids, and their in vitro biological activities were evaluated. It was found that most compounds displayed good to moderate in vitro antitumor activities against six human cancer cells. Especially, the antitumor activities of compound 7b, with the IC50 values of 5.51-9.25 μmol/L range against all tested cancer cells, were superior to those of FTS and sorafenib, and compound 7b could selectively inhibit the proliferation of tumor ceils but not that of human normal cell. Furthermore, compound 7b significantly induced SMMC-7721 cell apoptosis in a dose-dependent manner.

关 键 词：法尼基硫代水杨酸 羟基肉桂酸 合成 细胞凋亡 抗肿瘤活性 

分 类 号：R914.5[医药卫生—药物化学]