Coumarin-based fluorescent ligands target mitochondrial G-quadruplexes for liver cancer growth suppression

Natural coumarins are important scaffolds in drug development due to their diverse biological activities. This study investigated coumarin-derived fluorescent ligands targeting mitochondrial DNA G-quadruplexes (mtG4s), which are emerging therapeutic targets in cancer research. Six coumarin derivatives (X-1 to X-6) were synthesized, with X-1 showing the strongest stabilizing ability (ΔT_m = 34 °C) and best fluorescence properties for mtG4s. X-1 may not only serve as a near-infrared (NIR) fluorescent tool for studying mtG4 dynamics but also induce mitochondrial dysfunctions in liver cancer cells, demonstrating potent anticancer activity. These findings highlighted the potential of mtG4-targeted strategies for cancer therapy, combining diagnostic and therapeutic functions. The study supported the development of coumarin-based ligands as dual-purpose agents for cancer therapy.