Cycloalkane analogues of sinefungin as EHMT1/2 inhibitors

被引：11
|
作者：
Liu, Qing [1 ,2 ,3 ]
Cai, Xiaoqing [2 ,3 ]
Yang, Dehua [2 ,3 ]
Chen, Yi [4 ]
Wang, Yafang [4 ]
Shao, Liming [1 ]
Wang, Ming-Wei [1 ,2 ,3 ,4 ]
机构：
[1] Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
[2] Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
[3] Natl Ctr Drug Screening, Shanghai 201203, Peoples R China
[4] Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2017年 / 25卷 / 17期
基金：
中国国家自然科学基金;
关键词：
Methyltransferase inhibitor; Cycloalkyl substituted analogue; Natural product; Sinefungin; METHYLTRANSFERASE G9A; GLP; METHYLATION; MECHANISM;
D O I：
10.1016/j.bmc.2017.06.032
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
A series of cycloalkyl substituted analogues of the natural product sinefungin lacking the amino-acid moiety was designed and synthesized. Two stereoisomers (6-R and 6-S) were separated and their bioactivities examined against EHMT1/2. Of which, compound 14d showed an inhibitory activity against EHMT1/2 (88.9%, IC50 = 21.8 mu M for EHMT1 and 77.6%, IC50 = 39.6 mu M for EHMT2, respectively) similar to that of sinefungin (100.0%, IC50 = 28.4 mu M for EHMT1 and 79.5%, IC50 = 30.1 mu M for EHMT2, respectively). Further studies against other methyltransferases such as PRMT1 showed no activity except that 12d displayed about 20% inhibition. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4579 / 4594
页数：16
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