Study of the prodrugs of peptide aldehydes as proteasome inhibitors  

肽醛类前药衍生物作为蛋白酶体抑制剂的研究(英文)

作　　者：Li-Qiang Han Yu-An Zhang Shu-Yang Yao Bo Xu Ze-Mei Ge Jing-Rong Cui Run-Tao Li 韩利强;张寓安;姚书扬;徐波;葛泽梅;崔景荣;李润涛(北京大学医学部天然药物及仿生药物国家重点实验室,药学院化学生物学系,北京100191)

机构地区：[1]State Key Laboratory of Natural and Biomimetic Drugs,Department of Chemical Biology,School of Pharmaceutical Sciences,Peking University Health Science Center,Beijing 100191,China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2012年第1期21-27,共7页中国药学（英文版）

基　　金：National Natural Science Foundation of China (Grant No.30772626)

摘　　要：To improve the stability of peptide aldehyde proteasome inhibitors, four peptide cycloacetal derivatives and two peptide heterocycle compounds were designed and synthesized. Their proteasome inhibition and in vitro anticancer activities were evaluated. The four peptide cycloacetal derivatives did not showed any activities, which demonstrated that this kind of cycloacetal derivatives might be suitable as prodrugs. The two peptide heterocycle compounds were found to show obvious activities at both enzyme and cell levels. These results provide us a new clue for the modification of peptide aldehyde proteasome inhibitors.为了提高经典的肽醛类蛋白酶体抑制剂的稳定性和生物利用度,我们设计合成了4个肽缩醛和2个肽杂缩醛衍生物,并对其进行了酶水平和体外抗肿瘤实验。结果显示,4个肽缩醛化合物几乎没有显示任何活性,表明此类化合物有用作前药的潜质。而2个肽杂缩醛化合物在酶水平和细胞水平均表现出明显的活性,则表明此类化合物可能不是通过前药的形式而发挥作用,进一步优化杂环的结构,有可能发现更好的蛋白酶体抑制剂。

关 键 词：Proteasome inhibitor ANTICANCER Peptide acetal derivative Prodrug principle 

分 类 号：R914[医药卫生—药物化学]