Polyphenols bind G4-Quadruplex structures and act as epigenetic modifiers with anti-cancer effects

G4-quadruplexes (G4s) are non-canonical structures of nucleic acids that develop in guanine rich regions of DNA and RNA. Due to their presence in oncogenic promoters and telomeres, G4s represent attractive targets in anticancer drug designs. G4s have also been the subject of recent research regarding their role as epigenetic modulators, supporting their participation in epigenetic processes that control gene expression. The development of small compounds that preferentially target G4s have led to a better understanding of how G4s control these mechanisms. Natural products have greatly contributed to the development of many successful examples of compounds with excellent anticancer activities. Therefore, it is important to investigate ligands targeting G4-quadruplexes in natural products such as dietary polyphenols and their derivatives. In this review, we provide an overview of the latest research on natural compounds, with especial emphasis on dietary polyphenols, as G4-quadruplex targeted ligands. We also discuss dietary polyphenols' structural chemistry that could facilitate their characterization as G4 ligands, highlighting their potential in the development of anticancer drugs. Finally, we explore polyphenols' potential mechanisms of action in regulating epigenetic machinery through G4 binding, thereby providing insights for the development of safe and effective therapeutical tools against cancer.