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 Jan 15;915:174514. doi: 10.1016/j.ejphar.2021.174514. Epub 2021 Sep 21.
1H-imidazo[4,5-f][1,10]phenanthroline (IPM713) is a type of tricyclic conjugated rigid planar structure with potential medical applications, but its anticancer activity has not yet been fully studied. In the present research, cells from seven different cancer types were used to study the anticancer effect, and IPM713 was found to inhibit the colorectal cancer cell line HCT116 most significantly, with a half maximal inhibitory concentration (IC) of 1.7 μM. The mechanisms by which IPM713 exerts anti-colorectal cancer activity were studied. IPM713 blocked the cell cycle in G0/G1 phase and induced apoptosis by suppressing the PI3K/AKT/mTOR axis. In addition, an acute toxicity test showed that the median lethal dose (LD) was above 5000 mg/kg. The findings of this research suggest that IPM713 can interfere with the PI3K/AKT/mTOR signaling pathway and might be a potential therapeutic candidate for the treatment of colorectal cancer.
1H-咪唑并[4,5-f][1,10]菲咯啉（IPM713）是一种具有潜在医学应用的三环共轭刚性平面结构，但它的抗癌活性尚未得到充分研究。在本研究中，使用来自七种不同癌症类型的细胞来研究抗癌效果，发现 IPM713 对结直肠癌细胞系 HCT116 的抑制作用最为显著，半数最大抑制浓度（IC）为 1.7 μM。研究了 IPM713 发挥抗结直肠癌活性的机制。IPM713 通过抑制 PI3K/AKT/mTOR 轴阻断细胞周期于 G0/G1 期并诱导细胞凋亡。此外，急性毒性试验表明，半数致死剂量（LD）高于 5000mg/kg。本研究结果表明，IPM713 可以干扰 PI3K/AKT/mTOR 信号通路，可能是治疗结直肠癌的潜在治疗候选药物。
