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MICHELANGELO GRUTTADAURIA

DNA-Binding and Anticancer Activity of Pyrene-Imidazolium Derivatives

  • Autori: Bonsignore, R.; Notaro, A.; Salvo, A.; Spinello, A.; Fiasconaro, G.; Terenzi, A.; Giacalone, F.; Keppler, B.; Giuliano, M.; Gruttadauria, M.; Barone, G.
  • Anno di pubblicazione: 2016
  • Tipologia: Articolo in rivista (Articolo in rivista)
  • OA Link: http://hdl.handle.net/10447/222903

Abstract

DNA-binding investigations showed that two different derivatives endowed with pyrene and imidazolium moieties, 1 and 2, strongly bind both double-stranded DNA and telomeric sequences in G-quadruplex (G4) conformation. The values of the DNA-binding constants indicate that 1 and 2 show preferential affinity for G4-DNA, of about one and two orders of magnitude, respectively. Moreover, 1 and 2 inhibit short and long-term proliferation of breast cancer cell lines in a time- and dose-dependent fashion. Remarkably, senescence assays indicate that telomeric G4-DNA is a possible biotarget for the cytotoxic activity of 2. Molecular dynamics simulations suggest that the stronger binding of 2 with G4-DNA and the related senescence induction, are a consequence of additional edge-to-face interactions with a base in the TTA loop.