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.
|Data di pubblicazione:||2016|
|Titolo:||DNA-Binding and Anticancer Activity of Pyrene-Imidazolium Derivatives|
|Citazione:||Bonsignore, R., Notaro, A., Salvo, A., Spinello, A., Fiasconaro, G., Terenzi, A., et al. (2016). DNA-Binding and Anticancer Activity of Pyrene-Imidazolium Derivatives. CHEMISTRYSELECT, 1(1), 6755-6761.|
|Digital Object Identifier (DOI):||10.1002/slct.201601502|
|Settore Scientifico Disciplinare:||Settore CHIM/03 - Chimica Generale E Inorganica|
|Appare nelle tipologie:||1.01 Articolo in rivista|