title: Divalent Naphthalene Diimide Ligands Display High Selectivity for the Human Telomeric G-quadruplex in K+Buffer.
abstract: 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.
authors.affiliation: School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.
authors.forename: Steven T G
authors.identifier: http://orcid.org/0000-0002-7635-8733
authors.initials: STG
authors.lastname: Street
authors.affiliation: Novartis Institutes for Biomedical Research, 250 Massachusetts Ave., Cambridge, Massachusetts, 02139, USA.
authors.forename: Donovan N
authors.initials: DN
authors.lastname: Chin
authors.affiliation: Novartis Institutes for Biomedical Research, Novartis Campus, 4002, Basel, Switzerland.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hollingworth
authors.affiliation: School of Physics, University of Bristol, HH Wills Physics Laboratory, Bristol, BS8 1TL, UK.
authors.forename: Monica
authors.initials: M
authors.lastname: Berry
authors.affiliation: Instituto de Parasitología y Biomedicina, Avenida del Conocimiento, s/n, 18016, Armilla, Granada, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Morales
authors.affiliation: School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.
authors.forename: M Carmen
authors.identifier: http://orcid.org/0000-0001-7307-2871
authors.initials: MC
authors.lastname: Galan
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D002021:Buffers; D002151:Calorimetry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D015195:Drug Design; D054856:G-Quadruplexes; D006367:HeLa Cells; D006801:Humans; D007094:Imides / Q000737:chemistry*; D008024:Ligands; D018613:Microscopy, Confocal; D009281:Naphthalenes / Q000737:chemistry*; D011188:Potassium / Q000737:chemistry*; D016615:Telomere / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002021:Buffers; D007094:Imides; D008024:Ligands; D009281:Naphthalenes; C542131:naphthalenediimide; D011188:Potassium
keywords: G-quadruplexes; antitumour agents; carbohydrates; drug design; molecular recognition