A team of researchers from the University of Aveiro (UA) published a scientific review article in the journal "Medicinal Research Reviews" exploring a little-known dimension of phosphonates, a family of chemical compounds with applications ranging from agriculture to human health.

Published in a high-impact scientific journal, the article explains how phosphonates intervene in brain biochemistry, starting with their darker origins as neurotoxic weapons and moving on to their contribution to the therapy of diseases such as Alzheimer's and ischemic brain injury.

The work, entitled "Phosphonates as Modulators of Brain Chemistry," is authored by researchers affiliated with the Department of Chemistry at UA and two research units. Susana Santos Braga, Nádia E. Santos, and Maria Almeida-Santos are members of the Associated Laboratory for Green Chemistry (LAQV-REQUIMTE), and Flávio F. Figueira and Filipe A. Almeida Paz are members of CICECO-Instituto de Materiais de Aveiro. Gathering scientific evidence produced in recent years, this study shows how phosphonates can play a much broader role in medicine than has traditionally been attributed to them, from osteoporosis medications like Alendronate (Fosamax) to antibiotics like fosfomycin, antivirals, and antitumor drugs.

Most phosphonates, particularly those used medicinally, have molecules too large to cross the membrane that protects the brain (blood-brain barrier). Some phosphonates, however, are able to do so, having gained notoriety for the worst reasons: potent toxic activity in brain tissue. But are all phosphonates bad for the brain? Could they go from villains to heroes with subtle tweaks to their structure? It is precisely this versatility that motivated UA researchers to look at these compounds from a new perspective: that of rational chemical design in neuroscience.

This review describes current knowledge about the interaction of phosphonates with biochemical processes in the central nervous system and analyzes their potential in areas such as Alzheimer's disease, Parkinson's disease, and recovery from ischemic stroke. More than presenting a new therapy, the article identifies research opportunities, discusses existing knowledge about structure-activity relationships, and points out the main scientific challenges that must be overcome for these molecules to find applications in neurology in the future.

This article represents another step in a line of research that the team has been developing over the last decade. Led by Susana Santos Braga and Filipe A. Almeida Paz, this team has contributed to deepening knowledge about the chemistry of phosphonates and bisphosphonates, their synthesis, and incorporation into three-dimensional materials such as MOFs (Metal-Organic Frameworks) with new biomedical applications. Their work is now an international reference in the field and has helped to identify new possibilities for a family of compounds whose versatility continues to surprise.

The central message is clear: despite being molecules studied for decades, phosphonates may still reveal unexpected properties and open new lines of research in diseases for which there are still few therapeutic options.

More information: https://onlinelibrary.wiley.com/doi/10.1002/med.70070