Premium
DNA‐Binding and Anticancer Activity of Pyrene‐Imidazolium Derivatives
Author(s) -
Bonsignore Riccardo,
Notaro Antonietta,
Salvo Anna Maria Pia,
Spinello Angelo,
Fiasconaro Giuseppe,
Terenzi Alessio,
Giacalone Francesco,
Keppler Bernhard K.,
Giuliano Michela,
Gruttadauria Michelangelo,
Barone Giampaolo
Publication year - 2016
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201601502
Subject(s) - dna , chemistry , pyrene , stereochemistry , g quadruplex , base pair , biochemistry , biophysics , biology , organic chemistry
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.