取代乙酸己(庚)硫酯类化合物的合成与体外抗肿瘤活性  

Synthesis and antitumor activity of S-hexyl(heptyl) substituted ethanethioate derivatives

作　　者：闻家辰[1] 姜涛[1] 包宇[2] 林贤俊[1] 王宛荞 刘丹[1] 赵临襄[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,辽宁沈阳110016

出　　处：《药学学报》2014年第3期352-358,共7页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81102323)

摘　　要：将天然产物apicidin分子中大环结构简化,并对锌离子结合区结构修饰,设计了两类取代乙酸己(庚)硫酯类化合物。所合成的26个化合物结构经1H NMR、IR、MS与HR-MS确证。采用MTT法与台盼蓝染色法对目标化合物进行了体外抗肿瘤活性筛选,药理结果显示,化合物II-1、II-3、II-6、II-13针对HL-60肿瘤细胞活性较好,IC50值达到微摩尔级,化合物II-7、II-8针对MCF-7肿瘤细胞的抑制作用优于阳性对照药伏立诺他,IC50值分别为3.19和6.29μmol·L-1。To simplify the macrocyclic fragment and to modify the zinc binding group of the natural product apicidin, two series of S-hexyl （heptyl） ethanethioate derivatives were designed and synthesized. Twenty-six compounds were synthesized and confirmed with 1H NMR, IR, MS and HR-MS spectrum, which were not reported. Take vorinostat as control, their antiporliferative activities against cancer cell lines, MCF-7 and HL-60, were tested with MTT assay or trypan blue staining method. Generally in both series it was found that, the chiral carbon atom at 7 position is not necessary, compounds II-1, II-3, II-6 and II-13 showed good activity on HL-60 cells in vitro, with the IC5o values less than 10 μmol·L^-1. II-7 and II-8 showed stronger activity against MCF-7 than Vorinostat, with the IC50 of 3.19 and 6.29 μmol·L^-1, respectively.

关 键 词：APICIDIN 硫酯 抗肿瘤活性 构效关系 

分 类 号：R916[医药卫生—药学]