Tri- and tetra-substituted naphthalene diimides as potent G-quadruplex ligands.
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.
Cuenca
Francisco
F
CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK.
Greciano
Olga
O
Gunaratnam
Mekala
M
Haider
Shozeb
S
Munnur
Deeksha
D
Nanjunda
Rupesh
R
Wilson
W David
WD
Neidle
Stephen
S
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D006801:Humans; D007094:Imides; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009281:Naphthalenes; D010618:Phenanthrolines / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D019098:Telomerase / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D007094:Imides; D008024:Ligands; D009281:Naphthalenes; D010618:Phenanthrolines; C542131:naphthalenediimide; D019098:Telomerase