Pyrazolopyrimidinones as a Novel Anticancer Therapy For Glioblastoma
We want to congratulate the members of our group for publishing the research article entitled “Development of Novel Anticancer Pyrazolopyrimidinones Targeting Glioblastoma” in ChemMedChem (July 2025). This research article focused on the cytotoxic activity of a novel family of pyrazolopyrimidinones in glioblastoma (GBM) cells and non-cancerous embryonic kidney cells, to investigate if pyrazolopyrimidinones have a potential as a selective glioblastoma therapy.
Pyrazolopyrimidinones are fused nitrogen-containing heterocyclic systems which are a scaffold in several bioactive drugs and drug candidates. 23 substituted pyrazolo[1,5-α]pyrimidinones were screened for cytotoxicity against the GBM U-251 MG cell line and the non-cancerous embryonic kidney HEK293 cell line to assess their potential as anti-GBM agents capable of selectivity for cancer cells. The article outlined a structure–activity relationship (SAR) study, HIT compound optimisation and mode of cell death studies.
Through analog synthesis of preliminary HIT compounds with varied structural substituents, a lead compound, 22, has been identified, which proved capable of inducing significant GBM cell death while having a marginal cytotoxicity against the non-cancerous cells. The results highlighted the potential of pyrazolo[1,5-α]pyrimidinones derivatives as a novel anti-GBM therapy, capable of selectively killing cancer cells. Furthermore, pyrazolo[1,5-α]pyrimidinones could provide a scaffold for further development of selective GBM therapies.
Please cite this article as: Byrne, K., Bednarz, N., McEvoy, C., Stephens, J. C., Curtin, J. F., & Kinsella, G. K. (2025). Development of Novel Anticancer Pyrazolopyrimidinones Targeting Glioblastoma. ChemMedChem, 20(20), e202500337. https://doi.org/10.1002/cmdc.202500337