4.7 Article

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

Journal

EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 915, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.ejphar.2021.174514

Keywords

Colorectal cancer; Cell cycle; Apoptosis; Phenanthroline derivative

Funding

  1. Key Research and Development Program of Gansu Province [21YF5FA112]
  2. Technological Innovation Guidance Program of Gansu Province [21CX6QA127]
  3. College Students' Innovation and Entrepreneurship Training Program of Lanzhou University [20210260002, 20210260009]

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IPM713 has been found to inhibit colorectal cancer cells and induce apoptosis, with its anticancer effect being most significant. Additionally, IPM713 regulates the cell cycle and the PI3K/AKT/mTOR signaling pathway. Acute toxicity tests have shown it to be relatively safe.
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 mu M. 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.

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