Pyrimidine-based compounds as promising anticancer agents targeting tumor cell senescence
Paula Carpintero-Fernández1,2, M Montserrat Martínez3, Alexander Carneiro-Figueira1,2
1CellCOM Research Group, Center for Research in Nanomaterials and Biomedicine (CINBIO) and Institute of Biomedical Research of Ourense-Pontevedra-Vigo (IBI), University of Vigo, The Galician Health Service, SERGAS, 36210 Vigo, Spain.
Molecular Therapy. Oncology
|February 3, 2026
Summary
Novel pyrimidine compounds (P12 and P14) show antitumor effects by inducing senescence and cell death in breast cancer and melanoma cells. These findings suggest potential for developing new pro-senescent anticancer therapies.
Area of Science:
- Medicinal Chemistry
- Cancer Biology
- Pharmacology
Background:
- The pyrimidine core is a key structure in bioactive molecules, including anticancer agents.
- Novel pyrimidine derivatives are being explored for therapeutic potential.
Purpose of the Study:
- To evaluate the antitumor activity of two novel 4,6-disubstituted-2-(4-morpholinyl) pyrimidines (P12 and P14).
- To investigate the mechanisms underlying their anticancer effects in breast cancer and melanoma cell lines.
Main Methods:
- Cell proliferation assays in 2D and 3D culture models.
- Cell-cycle analysis and gene transcription studies.
- Senescence and senescence-associated secretory phenotype (SASP) evaluation.
Main Results:
- Compounds P12 and P14 significantly reduced cell proliferation in tested cancer cells.
- These pyrimidines induced cell-cycle delay and a senescent-like phenotype.
- Changes in SASP patterns and induction of cell death were observed.
Conclusions:
- Pyrimidine derivatives P12 and P14 exhibit promising antitumor properties.
- They act by inducing cellular senescence and potentially distinct cell death pathways.
- These compounds represent potential lead candidates for developing pro-senescent anticancer drugs.
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