新型法尼基硫代水杨酰胺衍生物的设计、合成及抗肿瘤活性  

Design,synthesis and antitumor activity of farnesylthiosalicylamide derivatives

作　　者：毛春芳[1,2] 徐辰俊 王雪敏[1,2] 李祥华[2] 张伟[2] 王新杨[2] 凌勇[1,2] 

机构地区：[1]江苏省南通卫生高等职业技术学校药学系,南通226001 [2]南通大学药学院,南通226001

出　　处：《中国药科大学学报》2015年第2期162-168,共7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：通过将法尼基硫代水杨酸(FTS)的羧基用各种胺进行胺化设计,合成得到11个法尼基硫代水杨酰胺衍生物(9a^9k),并对它们进行了体外抗肿瘤活性评价。实验表明其中的8个化合物对5种人肿瘤细胞具有较强的抗增殖活性,其中,化合物9k的细胞增殖抑制活性最强,对5种肿瘤细胞的IC50范围达6.05~8.16μmol/L,优于阳性对照FTS,与索拉非尼相当。此外,化合物9k可下调细胞内凋亡抑制蛋白Bcl-2的水平并上调促凋亡蛋白Bax和caspase-3,提示该化合物具有显著诱导肿瘤细胞凋亡的作用。A series of farnesylthiosalicylamide derivatives （9a-9k） were designed and synthesized via condensating the carboxyl of farnesyhhiosalicylic acid（FTS） with different amines, and the in vitro biological activity was evaluated. It was observed that eight of them displayed strong antitumor activity against five human cancer cells in vitro. Notably, compound 9k exhibited the most active with the ICs0 values of 6.05-8.16 μmol/L range against the tested cancer cells, which were superior to those of FTS and even comparable to that of sorafenib in vitro. In addition, compound 9k down-regulated the protein of Bcl-2 and increased the expression levels of Bax and caspase-3 proteins, indicating that compound 9k could induce tumor cell apoptosis.

关 键 词：法尼基硫代水杨酰胺 衍生物 合成 抗肿瘤活性 细胞凋亡 

分 类 号：R914.5[医药卫生—药物化学] R965[医药卫生—药学]