DNA‐Binding and Anticancer Activity of Pyrene‐Imidazolium Derivatives

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.