The G-quadruplex (G4) DNA, which has been developed as a potential anticancer 
target in drug screening and design, plays a crucial role in the oncogene 
transcription and translation. Tanshinone IIA derivatives with a planar 
heterocycle structure may function as G4 stabilizers. We present an innovative 
case of imidazole-based tanshinone IIA derivatives (1-8) especially compound 4 
that improve the selectivity and the binding affinity with G4 DNA and enhance 
the target tumor inhibition. Cellular and in vivo experiments indicate that the 
tanshinone IIA derivative 4 inhibits the growth, metastasis, and angiogenesis of 
triple-negative breast cancer cells possibly through the stabilization of 
multiple G4 DNAs (e.g., c-myc, K-ras, and VEGF) to induce DNA damage. Further 
investigation of the intermolecular interaction and the molecular docking 
indicates that tanshinone IIA derivatives have better selective binding 
capability to various G4 DNAs than to double-stranded DNA. These findings 
provide guidance in modifying the molecular structures of tanshinone IIA 
derivatives and reveal their potential to function as specific G4 stabilizers.