Synthesis of Hemiprotonic Phenanthroline-Phenanthroline+ Compounds with both Antitumor and Antimicrobial Activity

Currently, cancer patients with microbial infection are a severe challenge in clinical treatment. To address the problem, we synthesized hemiprotonic compounds based on the unique structure of hemiprotonic nucleotide base pairs in a DNA imotif. These compounds were produced from phenanthroline (ph) dimerization with phenanthroline as a proton receptor and ammonium as a donor. The biological activity shows that the compounds have a selective antitumor effect through inducing cell apoptosis. The molecular mechanism could be related to specific inhibition of transcription factor PLAGL2 of tumor cells, assessed by transcriptomic analysis. Moreover, results show that the hemiprotonic ph-ph(+) has broad-spectrum antibacterial and antifungal activities, and drug-resistant bacteria, including methicillin-resistant Staphylococcus aureus, are sensitive to the compound. In animal models of liver cancer with fungal infection, the ph-ph(+) retards proliferation of hepatoma cells in tumor-bearing mice and remedies pneumonia and encephalitis caused by Cryptococcus neoformans. The study provides a novel therapeutic candidate for cancer patients accompanied by infection.

Automated summary

The synthesized hemiprotonic compounds in this study have selective antitumor, antibacterial, and antifungal activities, possibly exerting antitumor effects by specific inhibition of transcription factor PLAGL2, and showing sensitivity to drug-resistant bacteria.