The Research Group of Bioorganic Chemistry and Biomaterials at the ICPF of the CAS has prepared a new series of fluorinated N‑acetylmannosamine (ManNAc) analogs and investigated their effects on an aggressive breast cancer cell line. The results were published in The Journal of Organic Chemistry.
Fluorine is an exceptionally important element in medicinal chemistry. Incorporating fluorine atoms into organic molecules can significantly alter their biological properties, stability, and cell-penetrating ability. In carbohydrates, fluorination can also affect cellular processes associated with the biosynthesis of glycoconjugates, which play important roles in cancer progression and metastasis.
In this study, the researchers synthesized a complete series of mono-, di-, and trifluorinated analogs of N-acetylmannosamine, a carbohydrate that serves as a key precursor of sialic acid. In addition to developing new synthetic routes, the team evaluated the biological activity of the prepared compounds using MDA-MB-231 cells, a model of aggressive triple-negative breast cancer. The results revealed that biological activity depends strongly on both the number and position of fluorine atoms within the monosaccharide. The most pronounced anticancer effect was observed for the trifluorinated analog, which inhibited cancer cell growth in several independent assays. Further experiments indicated that this compound induces DNA damage and triggers apoptosis, a form of programmed cell death.
The study not only provides new insights into the impact of fluorination on the biological properties of carbohydrates but also expands the potential of fluorinated glycomimetics as promising scaffolds for the development of novel anticancer agents. The research was carried out in collaboration with scientists from the Masaryk Memorial Cancer Institute.
- Krčil A., Šutvajová L., Hamala V., Císařová I., Kurfiřt M., Červenková Šťastná L., Bernášková J., Hrstka R., Karban J.: Synthesis and Antiproliferative Activity of Fluorinated N‑Acetylmannosamine Analogs. J. Org. Chem. 2026, 91(13), 4645–4656. doi.org/10.1021/acs.joc.5c03084