Dismantling self-assembly of light-illuminating AIE-based rotor probes via G-quadruplex DNA sensing as anti-cancer therapeutic.

G-quadruplex (G4) DNAs are regarded as prospective anti-cancer therapeutic targets due to their crucial regulatory functions in cancer genesis, replication, and growth in human cells. Recently, small molecule-based self-assembled rotor ligands have been shown to recognize G4 structures and have anti-cancer properties. Inspired by their expanding utility, we developed and synthesized three small molecule-based rotor ligands based on the xanthone chromophore, namely BVX, BMVX, and BHVX, and studied their photophysical and supramolecular characteristics, DNA recognition ability, and anti-cancer potential. Interestingly, one of the synthesized compounds, BMVX exhibited impressive aggregation-induced emission (AIE) activity in an aqueous environment. It specifically interacts with and stabilizes the c-KIT G4 DNA structure (Kd = 0.44-0.53 × 10-6 M, ΔTm = >15 °C) compared to other G4 and non-G4 structures in vitro. Notably, the self-assembled aggregates of BMVX disintegrated upon interaction with G4, resulting in a significant dampening of the fluorescence emission signal. BMVX binds to c-KIT G4 DNA using an end-stacking binding mechanism with a molar binding ratio of 1 : 1. BMVX showed anti-cancer action (IC50 = 8.27 ± 1.01 µM) in human hepatocellular carcinoma Huh-7 cells. It also caused cytotoxicity by halting the cell cycle at the G2/M phase via apoptotic pathways. Overall, these studies provide a potential blueprint for the creation of next-generation supramolecular G4 binders with anti-cancer properties.