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

Francisco Cuenca; Olga Greciano; Mekala Gunaratnam; Shozeb Haider; Deeksha Munnur; Rupesh Nanjunda; W David Wilson; Stephen Neidle

doi:10.1016/j.bmcl.2008.01.050

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

Bioorg Med Chem Lett. 2008 Mar 1;18(5):1668-73. doi: 10.1016/j.bmcl.2008.01.050. Epub 2008 Jan 18.

Authors

Francisco Cuenca¹, Olga Greciano, Mekala Gunaratnam, Shozeb Haider, Deeksha Munnur, Rupesh Nanjunda, W David Wilson, Stephen Neidle

Affiliation

¹ CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK.

PMID: 18243701
DOI: 10.1016/j.bmcl.2008.01.050

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemistry*
Antineoplastic Agents / metabolism*
Antineoplastic Agents / pharmacology
Cell Line, Tumor
Fluorescence Resonance Energy Transfer
G-Quadruplexes*
Humans
Imides
Ligands
Models, Molecular
Molecular Structure
Naphthalenes
Phenanthrolines / chemistry*
Phenanthrolines / metabolism*
Phenanthrolines / pharmacology
Telomerase / antagonists & inhibitors

Substances

Antineoplastic Agents
Imides
Ligands
Naphthalenes
Phenanthrolines
naphthalenediimide
Telomerase