Researchers from the Faculty of Sciences of the University of Porto (FCUP) have developed an antioxidant with the potential to become a drug to combat neurodegenerative diseases, it was announced this Tuesday.
In the study, published at the Journal of Medicinal Chemistrythe researchers describe the development of a “drug candidate” antioxidant for neurodegenerative diseases.
Cited in the FCUP statement, researcher Fernanda Borges clarified that to combat the changes caused by ‘stress’ in the mitochondria, an oxidant “must have, in its construction, a perfect set of parts to be able to cross the cell and mitochondrial membrane and thus reach this component of cells, essential to life”.
Like a Lego game, the researchers tested several pieces and were able to identify “an ideal piece that allows, after chemical modulation, to obtain innovative antioxidants targeted at the mitochondria, with low toxicity and with a neuroprotective effect”.
At the beginning of this construction is the structure of a natural antioxidant: the caffeic acidwhich is present in coffee, fruit and vegetables.
However, this type of antioxidant “cannot reach the mitochondria, and also does not have physicochemical properties that guarantee adequate bioavailability”, and can be “easily excreted”, clarified the researcher from the Center for Research in Chemistry at the University of Porto ( CIQUP).
In this sense, the team tested different parts to take caffeic acid to the mitochondria and which, at the same time, replaced the triphenylphosphonium cation which, despite being the “most used to guarantee the entry of a compound” into the mitochondria, can become “toxic to cells”.
“We had to ensure that the parts introduced were not toxic. For this, we used two cell lines in this study: one neuronal and one hepatic – because we would also have to assess whether the antioxidants caused damage to the liver, which is our main sensor of toxicity”, maintained Fernanda Borges.
After several attempts, the part that showed the “best results” was the isoquinoline-derived cation.
“We were able to obtain an antioxidant that enters the mitochondria, but does not cause toxic damage,” added the researchers, noting that this antioxidant revealed a “neuroprotective effect on cells”.
As part of the Pessoa Programme, of the Foundation for Science and Technology (FCT), the researchers will now, in partnership with the University of Montpellier (France), test the effectiveness of these antioxidants in ‘in vivo’ models.
The study, which is the result of more than 10 years of research focused on the development of new antioxidants, involved the collaboration of researchers from the Faculty of Pharmacy of the University of Porto, the Center for Neurosciences and Cell Biology of the University of Coimbra and the University of Santiago de Compostela, Spain.
Portuguese // 
