Bis-indole derivatives with antitumor activity turn out to be specific ligands of human telomeric G-quadruplex

被引：29

作者：

Amato, Jussara ^{[1
]}

Iaccarino, Nunzia ^{[1
]}

Pagano, Bruno ^{[1
]}

Morigi, Rita ^{[2
]}

Locatelli, Alessandra ^{[2
]}

Leoni, Alberto ^{[2
]}

Rambaldi, Mirella ^{[2
]}

Zizza, Pasquale ^{[3
]}

Biroccio, Annamaria ^{[3
]}

Novellino, Ettore ^{[1
]}

Randazzo, Antonio ^{[1
]}

机构：

[1] Univ Naples Federico II, Dept Pharm, Via D Montesano 49, I-80131 Naples, Italy

[2] Univ Bologna, Dept Pharm & Biotechnol FaBiT, Bologna, Italy

[3] Regina Elena Inst Canc Res, Expt Chemotherapy Lab, Rome, Italy

来源：

FRONTIERS IN CHEMISTRY | 2014年 / 2卷

关键词：

G-quadruplex; anticancer activity; telomeric damage; thermal stabilization; phenanthroline derivatives; pyridine derivatives; DNA-DAMAGE; SMALL-MOLECULE; INHIBITION; DISCOVERY; BINDING;

D O I：

10.3389/fchem.2014.00054

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Bis-indolinone derivatives having either 2,6-disubstituted pyridine core (1a and 1b) or 1,10-disubstituted phenanthroline core (2a and 2b), already known to have antitumor activity, have been tested as potential G-quadruplex binders. Compounds 2a and 2b are able to selectively stabilize G-quadruplex over duplex DNA, and also to discriminate among different G-quadruplex structures, having a particular affinity for the parallel form of the human telomeric G-quadruplex. Both compounds are also able to induce telomeric DNA damage that may explain the activity of these compounds.

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页数：8

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