那可丁衍生物合成及其作为微管干扰药物的生物学评估(英文)  

Synthesis and biological evaluation of noscapine analogues as microtubule-interfering agents

作　　者：戴厚玲[1] 郑剑斌[1] 林敏[1] 郑静[1] 周福生[2] 董肖椿[2] 郭磊[1] 刘建文[1] 闻韧[1,2] 

机构地区：[1]华东理工大学药学院,上海市新药设计重点实验室,上海200237 [2]复旦大学药学院,上海201203

出　　处：《药学学报》2012年第10期1347-1357,共11页Acta Pharmaceutica Sinica

基　　金：supported by the National Science Foundation of China(21102044);Shanghai Committee of Science and Technology(11DZ2260600)

摘　　要：以2-羟基-3-甲氧基苯甲醛为原料,经13步反应合成了26个那可丁衍生物。以HL-60细胞为靶细胞,采用MTT法进行了初步的体外抗肿瘤活性研究。结果表明,大多数化合物对HL-60细胞株显示出较好的抑制活性和对微管聚合的抑制作用。优选出的化合物31对HL-60细胞株以及微管聚合的抑制活性是那可丁的3倍并诱导HL-60细胞在G2/M期累积,这为那可丁及其衍生物的抗肿瘤活性构效关系的研究打下了基础,值得进一步研究。A series of noscapine analogues have been synthesized via 13-step reaction starting from 2- hydroxy-3-methoxybenzaldehyde. Anti-tumor activities of these compounds were evaluated against HL-60 cell lines in vitro by the standard MTT assay. It was found that most of these derivatives showed appreciable inhibitory activity against HL-60 and tubulin polymerization. The results also indicated that the potency of compound 31 is about three times more than that of noscapine against HL-60 cell line and tubulin polymerization Moreover, it induced a massive accumulation of cells in GE/M phase. These results showed noscapine and its derivatives were worth to be intensively studied further.

关 键 词：那可丁 微管 细胞毒活性 微管干扰药物 

分 类 号：R916[医药卫生—药学]