三尖杉酯碱衍生物的设计、合成与活性研究
Design,synthesis and activities of harringtonine derivatives
时旭 1赵常旭 1张振 1李颖 1陈国良1
作者信息
- 1. 沈阳药科大学制药工程学院,辽宁沈阳 110016
- 折叠
摘要
目的 设计合成三尖杉酯碱衍生物并评价其对HL-60细胞的抗增殖活性.方法 以三尖杉碱为起始原料,经亲核取代、还原、Mitsunobu等反应合成目标化合物LY-1～LY-15.采用台盼蓝染色法测试目标化合物对HL-60细胞的抗增殖活性.结果与结论 共合成15个未见文献报道的三尖杉酯碱衍生物,其结构均经ESI-MS、1H-NMR谱确证.活性测试结果表明三尖杉酯碱类化合物对HL-60细胞的抗增殖作用较强,其中化合物LY-1活性最强,IC50值为3.54 μmol·L-1,值得进一步研究.
Abstract
In order to discover compounds with good anti-leukemic activity,a total of fifteen harringtonine derivatives were designed and synthesized and their anti-proliferative activity on HL-60 cells were evaluated.The target compounds LY-1-LY-15 were synthesized by nucleophilic substitution,reduction and Mitsunobu reaction using cephalotaxine as the starting material.The structures of the target compounds were confirmed by ESI-MS and 1H-NMR spectra.The anti-proliferative activities of the target compounds against HL-60 cells were tested by Trypan blue staining method.Compound LY-1 showed the strongest inhibitory activity against HL-60 cells with IC50 value of 3.54 μmo1·L-1,which was worthy of further study.
关键词
急性髓系细胞性白血病/三尖杉酯碱/HL-60/衍生物Key words
AML/harringtonine/HL-60/derivative引用本文复制引用
出版年
2024
NETL
NSTL
万方数据