Synthesis of fluorinated imidazole[4,5f][1,10]phenanthroline derivatives as potential inhibitors against the proliferation of liver cancer cells by inducing apoptosis via DNAdamage.

Phenanthroline derivatives containing fluorinated imidazole ring are effective anti-neoplastic agents. Herein, a series of fluorinated imidazole[4,5f][1,10] phenanthroline derivatives have been synthesized and investigated as potential inhibitors against the growth of liver cancer cells. The in vitro antitumor activity of targeted compounds have been evaluated by using MTT assay, and results showed that 4 exhibited excellent inhibitory effect against the growth of various tumor cells, particularly for HepG2 cells, with IC 50 value of approximately 0.29 μM. This result has been further confirmed by colony formation assay, showing that 4 suppressed the proliferation of HepG2 cells. Moreover, cell apoptosis (AO/PI dual staining and flow cytometry) analyses as well as comet assay showed that 4 may induce apoptosis of HepG2 cells through triggering DNA damage. Furthermore, the in vivo anti-tumor activity were evaluated on zebrafish bearing HepG2 cells showed that 4 can observably block the growth of liver cancer cells. All in together, these compounds, particularly 4, may be developed as a potential agent to treat liver cancer in the future.