Synthesis and biological activity of 1H-imidazo[4,5-f][1,10]phenanthroline as a potential antitumor agent with PI3K/AKT/mTOR signaling

Shujian Hu; Wantong Ma; Junyi Wang; Zhongkun Zhou; Yunhao Ma; Rentao Zhang; Kangjia Du; Hao Zhang; Mengze Sun; Xinrong Jiang; Hongyuan Tu; Xiaoliang Tang; Xiaojun Yao; Peng Chen

doi:10.1016/j.ejphar.2021.174514

Synthesis and biological activity of 1H-imidazo[4,5-f][1,10]phenanthroline as a potential antitumor agent with PI3K/AKT/mTOR signaling

Eur J Pharmacol. 2022 Jan 15:915:174514. doi: 10.1016/j.ejphar.2021.174514. Epub 2021 Sep 21.

Authors

Shujian Hu¹, Wantong Ma¹, Junyi Wang², Zhongkun Zhou¹, Yunhao Ma¹, Rentao Zhang¹, Kangjia Du¹, Hao Zhang¹, Mengze Sun¹, Xinrong Jiang¹, Hongyuan Tu¹, Xiaoliang Tang³, Xiaojun Yao⁴, Peng Chen⁵

Affiliations

¹ School of Pharmacy, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
² College of Science and Technology, Wenzhou-Kean University, 88 Daxue Road, Wenzhou, 325060, PR China.
³ College of Chemistry and Chemical Engineering, Lanzhou University, 222 Tianshui South Road, Lanzhou, 730000, PR China.
⁴ Macau Institute for Applied Research in Medicine and Health, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, PR China.
⁵ School of Pharmacy, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China. Electronic address: chenpeng@lzu.edu.cn.

PMID: 34560078
DOI: 10.1016/j.ejphar.2021.174514

Abstract

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 (IC₅₀) 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 (LD₅₀) 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.

Keywords: Apoptosis; Cell cycle; Colorectal cancer; Phenanthroline derivative.

MeSH terms

Phosphatidylinositol 3-Kinases*