Tri- and tetra-substituted naphthalene diimides as potent G-quadruplex ligands

被引:119
|
作者
Cuenca, Francisco [1 ]
Greciano, Olga [1 ]
Gunaratnam, Mekala [1 ]
Haider, Shozeb [1 ]
Munnur, Deeksha [1 ]
Nanjunda, Rupesh [2 ]
Wilson, W. David [2 ]
Neidle, Stephen [1 ]
机构
[1] Univ London, Sch Pharm, CRUK Biomol Struct Grp, London WC1N 1AX, England
[2] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA
关键词
G-quadruplex; telomere; telomerase inhibition;
D O I
10.1016/j.bmcl.2008.01.050
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of tri- and tetra-substituted naphthalene diimides have been designed and synthesized. Several compounds show exceptional affinity for telomeric G-quadruplex DNA in classical and competition FRET assays and SPR studies. They inhibit telomerase in the TRAP assay, and show potent senescence-based short-term anti-proliferative effects on MCF7 and A549 cancer cell lines, and localize in the nucleus and particularly the nucleolus of MCF7 cells. (c) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1668 / 1673
页数:6
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