Synthesis and anticancer evaluations of novel 1H-imidazole [4,5-f][1,10] phenanthroline derivative for the treatment of colorectal cancer

• DOI: 10.1016/j.ejphar.2022.175120
• Publication Date: 2022-06-23T15:20:03Z
• Authors: Shujian Hu; Wantong Ma; Junyi Wang; Yunhao Ma; Zhongkun Zhou; Rentao Zhang; Kangjia Du; Hao Zhang; Mengze Sun; Xinrong Jiang; Hongyuan Tu; Xiaoliang Tang; Xiaojun Yao; Peng Chen
• Keywords: Imidazoles; Antineoplastic Agents; Apoptosis; HCT116 Cells; 3. Good health; Molecular Docking Simulation; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; 0302 clinical medicine; Cell Line, Tumor; Humans; Colorectal Neoplasms; Cell Proliferation; Phenanthrolines

1H-imidazole [4,5-f][1,10] phenanthroline is a promising chemical structure for cancer treatment. Herein, we synthesized a novel 1H-imidazole [4,5-f][1,10] phenanthroline derivative named IPM714 and found it exhibited selectively colorectal cancer (CRC) cells inhibitory activities, with half maximal inhibitory concentration (IC50) of 1.74 μM and 2 μM in HCT116 cells and SW480 cells, respectively. The present study is intended to explore the cytotoxicity of IPM714 in cancer cells of various types and its anticancer mechanism in vitro. Cellular functional analyses indicated IPM714 can arrest HCT116 cell cycle in S phase and induce apoptosis in HCT116 and SW480 cells. Western blot and molecular docking showed that IPM714 may suppress PI3K/AKT/mTOR pathway to inhibit cell proliferation and regulate cell cycle as well as apoptosis. This study proved IPM714 to be a promising drug in CRC therapy.