Synthesis, docking studies and antitumor activity of phenanthroimidazole derivatives as promising c-myc G-quadruplex DNA stabilizers.

Phenanthroimidazole derivatives containing phenanthroline and imidazole heterocyclic aromatic rings are effective agents to inhibit tumor cell growth. Herein, halogen element-modified imidazo[4,5f][1,10]phenanthroline derivatives 1-6 (1, 4-fluorophenyl; 2, 4-chlorophenyl; 3, 4-bromobenyl; 4, 2,3-dichlorophenyl; 5, 3,4-dichlorophenyl; and 6, 2,4-dichlorophenyl) were synthesized, and their antitumor activities were investigated. All of the compounds, especially 4, exhibited an excellent inhibitory effect against nasopharyngeal carcinoma CNE-1 cells. This effect was better than that of doxorubicin. Compound 4 also markedly blocked the proliferation of the CNE-1 cells in a zebrafish xenograft model. The antitumor mechanisms might be attributed to apoptosis induction, which triggered ROS-mediated DNA damage and generated mitochondrial dysfunction by stabilizing c-myc G-quadruplex DNA structure. Results indicated that phenanthroimidazole derivatives could act as promising anticancer agents.