School of Pharmacy, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
College of Science and Technology, Wenzhou-Kean University, 88 Daxue Road, Wenzhou, 325060, PR China.
Eur J Pharmacol. 2022 Aug 5;928:175120. doi: 10.1016/j.ejphar.2022.175120. Epub 2022 Jun 23.
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 (IC) 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.
1H-咪唑[4,5-f][1,10]菲咯啉是一种有前途的癌症治疗化学结构。在此，我们合成了一种新型的 1H-咪唑[4,5-f][1,10]菲咯啉衍生物，命名为 IPM714，并发现它对结直肠癌细胞（CRC）具有选择性抑制活性，在 HCT116 细胞和 SW480 细胞中的半最大抑制浓度（IC）分别为 1.74 μM 和 2 μM。本研究旨在探讨 IPM714 在各种类型癌细胞中的细胞毒性及其在体外的抗癌机制。细胞功能分析表明，IPM714 可使 HCT116 细胞周期停滞在 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，并调节细胞周期和凋亡。这项研究证明了 IPM714 是 CRC 治疗的一种有前途的药物。
