title: Hybrid ligand-alkylating agents targeting telomeric G-quadruplex structures.
abstract: The synthesis, physico-chemical properties and biological effects of a new class of naphthalene diimides (NDIs) capable of reversibly binding telomeric DNA and alkylate it through an electrophilic quinone methide moiety (QM), are reported. FRET and circular dichroism assays showed a marked stabilization and selectivity towards telomeric G4 DNA folded in a hybrid topology. NDI-QMs' alkylating properties revealed a good reactivity on single nucleosides and selectivity towards telomeric G4. A selected NDI was able to significantly impair the growth of melanoma cells by causing telomere dysfunction and down-regulation of telomerase expression. These findings points to our hybrid ligand-alkylating NDIs as possible tools for the development of novel targeted anticancer therapies.
authors.affiliation: Dipartimento di Chimica, Università di Pavia, V.le Taramelli 10, 27100 Pavia, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Doria
authors.forename: Matteo
authors.initials: M
authors.lastname: Nadai
authors.forename: Marco
authors.initials: M
authors.lastname: Folini
authors.forename: Marco
authors.initials: M
authors.lastname: Di Antonio
authors.forename: Luca
authors.initials: L
authors.lastname: Germani
authors.forename: Claudia
authors.initials: C
authors.lastname: Percivalle
authors.forename: Claudia
authors.initials: C
authors.lastname: Sissi
authors.forename: Nadia
authors.initials: N
authors.lastname: Zaffaroni
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
authors.forename: Anna
authors.initials: A
authors.lastname: Artese
authors.forename: Sara N
authors.initials: SN
authors.lastname: Richter
authors.forename: Mauro
authors.initials: M
authors.lastname: Freccero
mesh_terms: D000477:Alkylating Agents / Q000737:chemistry* / Q000494:pharmacology; D000478:Alkylation; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D054856:G-Quadruplexes; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D016615:Telomere / Q000737:chemistry* / Q000187:drug effects
chemical_list: D000477:Alkylating Agents; D008024:Ligands