AUTHOR=Pagano Alessia , Iaccarino Nunzia , Abdelhamid Mahmoud A. S. , Brancaccio Diego , Garzarella Emanuele U. , Di Porzio Anna , Novellino Ettore , Waller Zoë A. E. , Pagano Bruno , Amato Jussara , Randazzo Antonio TITLE=Common G-Quadruplex Binding Agents Found to Interact With i-Motif-Forming DNA: Unexpected Multi-Target-Directed Compounds JOURNAL=Frontiers in Chemistry VOLUME=6 YEAR=2018 URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2018.00281 DOI=10.3389/fchem.2018.00281 ISSN=2296-2646 ABSTRACT=

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.