Oxidation-responsive G-quadruplex ligand for selective inhibition of the proliferation of tumour cells.

Tumour cells show a higher level of reactive oxygen species (ROS) than normal cells. On the basis of this difference, we designed an oxidation-responsive G-quadruplex proligand PDS-B by installing borolanylbenzyls on a well-known pyridostatin (PDS) ligand PDS-S to response high level ROS in tumour cells. The rapid oxidative degradation of the proligand to its active form PDS-S in the presence of H2O2 confirms the oxidation-responsive design. According to Förster resonance energy transfer (FRET) assays, circular dichroism (CD) spectra and confocal fluorescence imaging, PDS-B stabilizes telomeric G4 structures after oxidation with H2O2 or intracellular ROS. Apoptosis assays and cell cycle assays showed significant selectivity of PDS-B in inhibiting the proliferation of tumour cells over normal cells through responses to a high level of ROS in the formers. Further assays confirmed higher level of relative Caspase-3 activity in tumour cells than normal cells, consequently the enhanced apoptosis of the tumour cells induced by PDS-B. In summary, the results demonstrate a modification approach to solve the poor selectivity of the G4 ligand in tumour cells and cytotoxicity in normal cells.