TY - JOUR
T1 - DNA-Binding and Anticancer Activity of Pyrene-Imidazolium Derivatives
AU - Salvo, Anna Maria Pia
AU - Giuliano, Michela
AU - Bonsignore, Riccardo
AU - Spinello, Angelo
AU - Gruttadauria, Michelangelo
AU - Giacalone, Francesco
AU - Notaro, Antonietta
AU - Terenzi, Alessio
AU - Barone, Giampaolo
AU - Terenzi, Alessio
AU - Salvo, Anna Maria Pia
AU - Keppler, Bernhard K.
AU - Notaro, Antonietta
AU - Spinello, Angelo
AU - Bonsignore, Riccardo
AU - Barone, Giampaolo
AU - Fiasconaro, Giuseppe
AU - Giacalone, Francesco
AU - Gruttadauria, Michelangelo
AU - Giuliano, Michela
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10447/222903
M3 - Article
VL - 1
SP - 6755
EP - 6761
JO - ChemistrySelect
JF - ChemistrySelect
SN - 2365-6549
ER -