Abstract
To address the growing health threat posed by drug-resistant pathogenic microorganisms, the development of novel antimicrobial medications with multiple mechanisms of action is in urgent demand. With traditional antibacterial drug resources challenging to push forward, developing new antibacterial drugs has become a hot spot in biomedical research. In this study, we tested the antibacterial activity of 119 phenanthridine derivatives via the antibacterial assay and obtained 5 candidates. The cytotoxicity assay showed one phenanthridine derivative, HCK20, was safe for mammalian cells below 125 µM. HCK20 was verified to possess significant antibacterial activity to Streptococcus spp., such as Streptococcus pneumoniae, Streptococcus agalactiae, Streptococcus suis, Streptococcus dysgalactiae, and Streptococcus equi with MICs ranging from 15 to 60 µM. Furthermore, we found that HCK20 probably achieved its bacterial inhibition by influencing the permeability of bacterial cell walls via interacting with Streptococcal penicillin-binding proteins (PBPs). Our results suggest that this phenanthridine derivative, HCK20, has great potential to become a novel antibacterial agent that can be a potent treatment for streptococcal infections.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Funding
This study was supported by grants from Hainan Province Science and Technology Special Fund (ZDYF2022XDNY236) and the Fundamental Research Funds for the Central Universities (KYTZ2023002).
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ZSD and ZSY performed the experiments, analyzed the data, and drafted the manuscript. WYT and FSR assisted with molecular docking analyses. ZYM and LS gave useful suggestions in writing the manuscript. CDZ provided the phenanthridone derivatives used in the experiments. LGJ guided the study throughout. All authors contributed to the article and approved the submitted version.
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Communicated by Yusuf Akhter.
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Zhang, S., Zhang, S., Wang, Y. et al. Discovery of novel phenanthridone derivatives with anti-streptococcal activity. Arch Microbiol 205, 371 (2023). https://doi.org/10.1007/s00203-023-03705-7
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DOI: https://doi.org/10.1007/s00203-023-03705-7