Synthesis of Fluorinated Imidazole[4,5f][1,10]phenanthroline Derivatives as Potential Inhibitors of Liver Cancer Cell Proliferation by Inducing Apoptosis via DNA Damage

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)‐1H‐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.

Synthesis, characterization, and cancer cell-selective cytotoxicity of mixed-ligand cobalt(iii) complexes of 8-hydroxyquinolines and phenanthroline bases

“…Due to their aromaticity and extended planarity, these ligands can avidly bind to DNA and function as anticancer agents when coordinated to a metal ion. 33,34 Consequently, a mixed-ligand formulation incorporating phen and HQ derivatives could yield compounds with cancer cell selectivity and cytotoxicity. We have recently reported a series of mixed-ligand copper( ii ) complexes of 8-hydroxyquinoline and its derivatives, demonstrating significant cytotoxicity against cancer cells.…”

Rhenium(I) Tricarbonyl Complexes of 1,10-Phenanthroline Derivatives with Unexpectedly High Cytotoxicity

“…The development of anticancer agents that exhibit numerous mechanisms of action is of great importance since such compounds may have the ability to overcome typical obstacles such as ineffectiveness toward tumors and drug resistance. , A promising strategy in drug development to increase the potential of anticancer drugs in exhibiting multiple mechanisms of action is the coordination of organic molecules with anticancer potential to various metals. With this in mind and the recent success of imidazo­[4,5- f ]­1,10-phenanthroline derivatives as prospective anticancer agents in colorectal and liver cancer, − we designed a small library of rhenium­(I) tricarbonyl complexes (Figure ) with N,N′ -bidentate imidazo­[4,5- f ]­1,10-phenanthroline derivative ligand systems, with systematic changes with N,S and aromatic motifs on the backbone, having an appended aqua ligand to evaluate their potentials as anticancer agents. Rhenium­(I) tricarbonyl complexes are usually kinetically inert, which will help increase the complex half-life to reach the target.…”