European Journal of Pharmacology ( IF 4.2 ) Pub Date : 2022-06-23 , DOI: 10.1016/j.ejphar.2022.175120 Shujian Hu 1 , Wantong Ma 1 , Junyi Wang 2 , Yunhao Ma 1 , Zhongkun Zhou 1 , Rentao Zhang 1 , Kangjia Du 1 , Hao Zhang 1 , Mengze Sun 1 , Xinrong Jiang 1 , Hongyuan Tu 1 , Xiaoliang Tang 3 , Xiaojun Yao 4 , Peng Chen 1
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.
中文翻译:
用于治疗结直肠癌的新型1H-咪唑[4,5-f][1,10]菲咯啉衍生物的合成及抗癌评价
1H-咪唑[4,5-f][1,10]菲咯啉是一种很有前途的癌症治疗化学结构。在此,我们合成了一种名为 IPM714 的新型 1H-咪唑 [4,5-f][1,10] 菲咯啉衍生物,发现它具有选择性的结直肠癌 (CRC) 细胞抑制活性,半数最大抑制浓度 (IC 50 ) 为 1.74在 HCT116 细胞和 SW480 细胞中分别为 μM 和 2 μM。本研究旨在探讨IPM714对各类癌细胞的细胞毒性及其体外抗癌机制。. 细胞功能分析表明 IPM714 可以将 HCT116 细胞周期阻滞在 S 期并诱导 HCT116 和 SW480 细胞凋亡。Western blot和分子对接表明,IPM714可能通过抑制PI3K/AKT/mTOR通路来抑制细胞增殖,调节细胞周期和细胞凋亡。该研究证明 IPM714 是一种有前途的 CRC 治疗药物。