Synthesis of Fluorinated Imidazole[4,5f][1,10]phenanthroline Derivatives as Potential Inhibitors of Liver Cancer Cell Proliferation by Inducing Apoptosis via DNA Damage |
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Authors: | Ming-Jun Bai Ning-Zhi Liu Yu-Ling Zhou Prof Jie Liu Jun Zou Prof Wei-Jun Tan Xiao-Ting Huang Prof Wen-Jie Mei |
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Affiliation: | 1. Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510430 China;2. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006 China
These authors contributed equally to this work.;3. Department of Pharmacy, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510430 China;4. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006 China;5. School of Food, Guangdong Pharmaceutical University, Guangzhou, 510006 China |
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Abstract: | Phenanthroline derivatives containing fluorinated imidazole ring are effective anti-neoplastic agents. Herein, a series of four fluorinated imidazole4,5f]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-imidazo4,5-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. |
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Keywords: | imidazole phenanthroline derivatives liver cancer apoptosis DNA damage |
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