3,6-二酰氨基吨酮衍生物的设计、合成及生物活性研究  

Design, synthesis and biological activities of novel 3,6-diamide xanthones

作　　者：李子谦[1] 冯腾垒 曹婷婷[1] 赵泷 周增辉[1] 申蕊[1] 马正月[1] 

机构地区：[1]河北大学药学院河北省药物质量分析控制重点实验室,河北保定071002

出　　处：《药学学报》2017年第7期1133-1139,共7页Acta Pharmaceutica Sinica

基　　金：国家"重大新药创制"科技重大专项资助项目(2012ZX09103-101-057);河北省科技厅重点基础研究专项(11966411D);河北大学基金(2014-06;2014-07)

摘　　要：本文报道了一类以G-四联体为靶点的新型3,6-二酰氨基吨酮衍生物的设计、合成及活性研究。分子对接显示该系列化合物均以π-π堆积和沟槽插入相结合的方式作用于人端粒G-四联体,且这一结合方式经荧光光谱与紫外光谱证实,并在荧光滴定中发现化合物10c和10d对于四联体DNA具有较强的亲和力和选择性。随后经MTT法测试了筛选的化合物对三种人癌细胞株的体外抗增殖活性,其半数抑制率达到了微摩尔级。另外,PCR stop实验表明化合物10c和10d能够有效抑制端粒酶的扩增能力。A series of novel xanthones with terminal amine substituents at xanthone＇s C3 and C6 positions were designed and synthesized as potential ligands for telomeric G-quadruplex DNA. All the compounds in this series were bound to telomeric G-quadruplex in a ＂thread intercalation＂ manner that illustrated both in molecular docking and spectrometric studies. Among them, 10 c and 10 d showed better binding abilities and specific affinity toward G-quadruplex DNA HTG21 over ct DNA in the fluorescence assay. The antiproliferative activities of four screened compounds were examined in three cancer cells by MTT in vitro, and their inhibitory effects were observed at low micromolar ranges. In addition, the PCR stop assay demonstrated that 10 c and 10 d effectively inhibited the amplification ability of telomerase.

关 键 词：吨酮 G-四联体 分子对接 荧光光谱 细胞毒性 

分 类 号：R916[医药卫生—药学]