Synthesis of Fluorinated Imidazole[4, 5f][1, 10]phenanthroline Derivatives as Potential Inhibitors of Liver Cancer Cell Proliferation by Inducing Apoptosis via DNA Damage. (24th November 2021) - Bai, Ming‐Jun
Abstract: Phenanthroline derivatives containing fluorinated imidazole ring are effective anti‐neoplastic agents. Herein, a series of four fluorinated imidazole[4, 5f][1, 10]phenanthroline derivatives were synthesized and investigated as potential inhibitors to fight 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 compound 4 (2‐(2, 3‐difluorophenyl)‐1 H ‐imidazo[4, 5‐ f ][1, 10]phenanthroline) exhibited excellent inhibitory effect against the growth of various tumor cells, particularly for HepG2 cells, with IC50 value of approximately 0.29 μM. This result has been further confirmed by colony formation assay, showing that compound 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 compound 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 compound 4 can observably block the growth of liver cancer cells. All in together, these compounds, particularly compound 4, may be developed as a potential agent to treat liver cancer in the future. Abstract : Blocking cancer cell growth : Fluorinated imidazole[4, 5f][1, 10]phenanthroline derivative 4 (shown) can effectively inhibit the growth of HepG2 cells by inducing apoptosis via DNA damage. Our findings provideguidance for further optimization of imidazole phenanthroline derivatives and the development of potential anticancer agents.