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

Selective G‐quadruplex ligands offer great promise for the development of anti‐cancer therapies. A novel series of divalent cationic naphthalene diimide ligands that selectively bind to the hybrid form of the human telomeric G‐quadruplex in K+ buffer are described herein. 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. Get into the groove…: A series of divalent naphthalene diimide ligands selectively bind to the human telomeric G‐quadruplex in K+ buffer. An imidazolium‐bearing mannoside conjugate is the most selective ligand discovered to date for this quadruplex structure, and a similarly selective methylpiperazine‐bearing ligand was more toxic to HeLa cancer cells than doxorubicin, but with three times less toxicity towards fetal lung fibroblasts WI‐38.