Researchers at IBS.GRANADA are developing compounds with therapeutic potential against triple-negative breast cancer.
The study, published in the journal Bioorganic Chemistry, identifies molecules capable of blocking a key interaction in the progression of this type of tumor.
A research team Led by the Granada Biosanitary Research Institute (ibs.GRANADA) and the University of Granada has developed new compounds capable of blocking a fundamental process in the progression of triple-negative breast cancer, one of the most aggressive cancer subtypes with the lowest response to current treatments.
The work, carried out in collaboration with the GENYO Center and the University of Bath (United Kingdom), has demonstrated that certain laboratory-designed molecules derived from the tetrahydroisoquinoline family can effectively interfere with the interaction between hyaluronic acid, a substance naturally present in our bodies, and the CD44 receptor, which is located on the surface of certain tumor cells. This union allows tumor cells to grow more rapidly and spread to other parts of the body, thus promoting the progression and spread of cancer in certain subtypes of breast cancer.
The research has focused on the triple negative breast cancer, a subtype that does not respond to conventional hormonal treatments or therapies targeting other common receptors, severely limiting therapeutic options. To study these compounds, the team used a widely validated laboratory model: MDA-MB-231 cells, representative of this tumor subtype and characterized by high expression of the CD44 receptor.
The designed compounds were evaluated using computational studies and tumor cell assays. The results showed that These new molecules bind effectively to the CD44 receptor, preventing its interaction with hyaluronic acid. and thus slowing the proliferation of tumor cells.
Furthermore, The effects were much smaller in cells with low CD44 expression, indicating a specific action of the compounds, a relevant aspect for the development of more selective and safe treatments. Other experiments, such as the use of CD44-blocking antibodies and assays with fluorescent hyaluronic acid, confirmed the proposed mechanism of action.
"This study provides a solid foundation for the development of even more active compounds, with the hope that they can advance to preclinical trials and, in the future, reach clinical practice," says Olga Cruz, co-principal investigator of the A03 Bioactive Molecules group at ibs.GRANADA, professor at the University of Granada, and principal investigator of the study.
These results open up new possibilities for the development of targeted therapies for breast cancer, especially in tumors that exhibit high expression of the CD44 receptor, an emerging biomarker of therapeutic interest.
The study has been funded by the Ministry of Science and Innovation (project PID2021.128109OB.I00), the European Regional Development Fund (ERDF), and the Andalusian Regional Government (project P18-RT-1679), as well as support from the British consortium HECBioSim, funded by the EPSRC.
About the group
El grupo Bioactive Molecules (A03) of the ibs.GRANADA focuses on the design and discovery of new substances with therapeutic interest, primarily focused on the development of antitumor agents. This interdisciplinary group integrates pharmaceutical chemists and biologists who combine synthetic chemistry techniques, computational analysis, and cellular assays to advance possible innovative cancer treatments..
More information about the group: https://www.ibsgranada.es/grupos-de-investigacion/a03-moleculas-bioactivas/
Bibliographic reference:
Chayah, M., Espejo-Román, J.M., Erviti-Marticorena, L., Huertas-Camarasa, F., Domene, C., Sánchez-Martín, R.M., Conejo-García, A., & Cruz-López, O. (2025). New N-Alkylketonetetrahydroisoquinoline derivatives exhibit antitumor effect by HA-CD44 interaction inhibition in MDA-MB-231 breast cancer. Bioorganic Chemistry, 156, 108212. https://doi.org/10.1016/j.bioorg.2025.108212
