Common G-quadruplex binding agents found to interact with i-motif-forming DNA: Unexpected multi-target-directed compounds

Alessia Pagano, Nunzia Iaccarino, Mahmoud A. S. Abdelhamid, Diego Brancaccio, Emanuele U. Garzarella, Anna Di Porzio, Ettore Novellino, Zoë A. E. Waller, Bruno Pagano, Jussara Amato, Antonio Randazzo

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)
28 Downloads (Pure)


G-quadruplex (G4) and i-motif (iM) are four-stranded non-canonical nucleic acid structural arrangements. Recent evidences suggest that these DNA structures exist in living cells and could be involved in several cancer-related processes, thus representing an attractive target for anticancer drug discovery. Efforts toward the development of G4 targeting compounds have led to a number of effective bioactive ligands. Herein, employing several biophysical methodologies, we studied the ability of some well-known G4 ligands to interact with iM-forming DNA. The data showed that the investigated compounds are actually able to interact with both DNA in vitro, thus acting de facto as multi-target-directed agents. Interestingly, while all the compounds stabilize the G4, some of them significantly reduce the stability of the iM. The present study highlights the importance, when studying G4-targeting compounds, of evaluating also their behavior toward the i-motif counterpart.
Original languageEnglish
Article number281
JournalFrontiers in Chemistry
Publication statusPublished - 24 Jul 2018

Cite this