Potent sirtuin inhibition with 1,2,5-trisubstituted benzimidazoles

被引：8
|
作者：
Yoon, Y. K. [1 ]
Osman, H. [2 ]
Choon, T. S. [1 ]
机构：
[1] Univ Sains Malaysia, Inst Res Mol Med, Minden 11800, Penang, Malaysia
[2] Univ Sains Malaysia, Sch Chem Sci, Minden 11800, Penang, Malaysia
来源：
MEDCHEMCOMM | 2016年 / 7卷 / 11期
关键词：
CRYSTAL-STRUCTURE; MECHANISM; SIR2; DEACETYLATION; NICOTINAMIDE; DERIVATIVES; MODULATION; DISCOVERY;
D O I：
10.1039/c6md00378h
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：
Two series of compounds were synthesized based on the benzimidazole scaffold. The compounds were subsequently screened for their SIRT1, SIRT2 and SIRT3 activities. Three of the compounds showed good inhibitory activity against SIRT2 in this study with the most potent compound ( 5i) having an IC50 value of 2.9 mu M. Molecular docking analysis demonstrated that 5i was able to inhibit SIRT2 by displacing the co-factor NAD(+) in the active site. This was further confirmed experimentally by ligand-NAD(+) competitive assay.
引用
收藏
页码：2094 / 2099
页数：6
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