Exploring the role of G-quadruplex DNA, and their structural polymorphism, in targeting small molecules for the design of anticancer therapeutics: Progress, challenges, and future directions

Selective stabilization of non-canonical G-quadruplex DNA structures by small molecules can be a potential target for anticancer therapeutics. The primary motivation for the molecular design of these G-quadruplex binders is to restrict the transcriptional machinery, which can impede cancer cell progression. This review article comprises the structural diversity of different G-quadruplex DNA, the design strategy for targeting these structures with small molecules, and various G-quadruplex binding ligands which have been expanded by the chemists and biologists over the past few decades. Further, the existence of G-quadruplex structures inside human cells, the significant challenges for designing these selective G-quadruplex binding ligands, current status, and progress towards achieving this goal have also been discussed.