Divalent Naphthalene Diimide Ligands Display High Selectivity for the Human Telomeric G-quadruplex in K+ Buffer

Selective G-quadruplexligands offer great promise for the development of anti-cancer therapies. A new class of cationic naphthalene diimideligands that selectively bind to the hybrid form of the human telomeric G-quadruplexin K+ buffer are described here. We demonstrate that an imidazolium-bearing mannoside-conjugate is the most selective ligand to date for this quadruplex against several other quadruplex and duplex structures. We also show that a similarly selective methylpiperazine-bearing ligand was more toxic to HeLa cancer cells than doxorubicin, whilst exhibiting three times less toxicity towards fetal lung fibroblasts WI-38.