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Designed a new family of molecules with high affinity with altered receptors in neurodegenerative diseases

Prof. Luque and his team joined an important study on the synthesis and three-dimensional quantitative structure–activity relationship (3D-QSAR) of a new family of bicyclic α-iminophosphonates endowed with relevant affinities for human brain I2-IR.

Imidazoline I2 receptors (I2-IR), widely distributed in the CNS and altered in patients that suffer from neurodegenerative disorders, are orphans from a structural point of view, and new I2-IR ligands are urgently required for improving their pharmacological characterization. Acute treatment in mice with a selected compound significantly decreased Fas-associated protein with death domain (FADD) in the hippocampus, a key signaling mediator of neuroprotective actions. Additionally, in vivo studies in the familial Alzheimer’s disease 5xFAD murine model revealed beneficial effects in behavior and cognition. These results are supported by changes in molecular pathways related to cognitive decline and Alzheimer’s disease. Therefore, bicyclic α-iminophosphonates are tools that may open new therapeutic avenues for I2-IR, particularly for unmet neurodegenerative conditions.

@UniBarcelona press release: https://www.ub.edu/web/ub/en/menu_eines/noticies/2020/03/059.html?

Reference Article: https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b02080#