Tetrasubstituted naphthalene diimide ligands with selectivity for telomeric G-quadruplexes and cancer cells

被引：89

作者：

Hampel, Sonja M. ^{[1
]}

Sidibe, Assitan ^{[2
]}

Gunaratnam, Mekala ^{[1
]}

Riou, Jean-Francois ^{[2
]}

Neidle, Stephen ^{[1
]}

机构：

[1] Univ London, Sch Pharm, CRUK Biomol Struct Grp, London WC1N 1AX, England

[2] Museum Natl Hist Nat, Biophys Lab, CNRS, INSERM,U655,UMR 7196, Paris, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 22期

关键词：

Quadruplex; Naphthalene diimide; Telomerase; Cancer; INTRAMOLECULAR G-QUADRUPLEX; TOPOISOMERASE-III-ALPHA; POTENTIAL INHIBITORS; STABILIZING LIGANDS; TUMOR-CELLS; K+ SOLUTION; C-MYC; DNA; TELOMESTATIN; BINDING;

D O I：

10.1016/j.bmcl.2010.09.066

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of tetrasubstituted naphthalene diimide compounds with N-methylpiperazine end groups has been synthesized and evaluated as G-quadruplex ligands. They have high affinity and selectivity for telomeric G-quadruplex DNA over duplex DNA. CD studies show that they induce formation of a parallel G-quadruplex topology. They inhibit the binding of hPOT1 and topoisomerase IIIa to telomeric DNA and inhibit telomerase activity in MCF7 cells. The compounds have potent activity in a panel of cancer cell lines, with typical IC50 values of similar to 0.1 mu M, and up to 100-fold lower toxicity in a normal human fibroblast cell line. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：6459 / 6463

页数：5

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