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

作　　者：时旭 赵常旭 张振 李颖[1] 陈国良[1] SHI Xu;ZHAO Changxu;ZHANG Zhen;LI Ying;CHEN Guoliang(School of Pharmaceutical Engineering,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学制药工程学院,辽宁沈阳110016

出　　处：《中国药物化学杂志》2024年第4期294-302,共9页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(82273793)。

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、1 H-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,IC_(50)值为3.54μmol·L^(-1),值得进一步研究。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 IC_(50) value of 3.54μmol·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 

分 类 号：R914[医药卫生—药物化学]