Targeting Quadruplex Nucleic Acids: The Bisquinolinium Saga

Abstract

G-quadruplexes (G4s) are non-canonical secondary structures that can form in single-stranded DNA and RNA sequences containing multiple guanine tracts. G4s can accommodate and be stabilized by small molecules (G4 ligands) that typically interact by π-stacking with their external quartets. Along these lines, numerous G4 ligands acting as probes and drug prototypes have been reported, but only a few meet the criteria of selectivity and affinity necessary to achieve efficient G4 targeting in cells. The present chapter is focused on bisquinolinium compounds comprising two quinolinium units, typically linked to a (hetero)aromatic dicarboxamide core and which represent the “gold standard” of G4 ligands. The seminal works that led to their design, the development of functional derivatives and of new analogues are described. In addition, a brief overview of their applications to imaging and covalent trapping of G4s in cells and of their therapeutic potential in treating cancer and other diseases is presented.KeywordsG-quadruplexesG4 ligandsBisquinolinium compoundsPDCPhenDC