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 downregulation of telomerase expression. These findings points to our hybrid ligand–alkylating NDIs as possible tools for the development of novel targeted anticancer therapies.

Hybrid ligand–alkylating agents targeting telomeric G-quadruplex structures

DORIA, FILIPPO;GERMANI, LUCA;PERCIVALLE, CLAUDIA;FRECCERO, MAURO
2012-01-01

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 downregulation of telomerase expression. These findings points to our hybrid ligand–alkylating NDIs as possible tools for the development of novel targeted anticancer therapies.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/385910
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 92
  • ???jsp.display-item.citation.isi??? 91
social impact