University of Porto (FCUP) Faculty of Sciences researchers have developed an antioxidant that could be a drug to fight neurodegenerative diseases, it was announced on Monday.
In a study published in the Journal of Medicinal Chemistry, the researchers describe the development of an antioxidant “drug candidate” for neurodegenerative diseases.
Quoted in the FCUP statement, researcher Fernanda Borges explains that in order to combat the changes caused by “stress” in mitochondria, the oxidant “must have in its design an ideal set of parts in order to be able to cross the cell and mitochondrial membranes and thus arrive at this component of the cells, necessary for life.”
Similar to a Lego game, the researchers tested several pieces and were able to identify “an ideal piece that allows, after chemical modulation, to produce innovative mitochondrial-targeted antioxidants with low toxicity and neuroprotective effects.”
At the beginning of this construction is the structure of a natural antioxidant: caffeic acid, which is present in coffee, fruits and vegetables.
However, this type of antioxidant “cannot reach the mitochondria, nor does it have the physicochemical properties to guarantee adequate bioavailability” and can “easily be excreted from the body,” said a researcher from the University of Porto Chemical Research Center (CIQUP). ).
In this sense, the team tested various parts to deliver caffeic acid to the mitochondria and at the same time replace the triphenylphosphonium cation, which, despite being “most commonly used to ensure the compound enters” into the mitochondria, can become “toxic to cells.”
“We had to make sure that the injected parts were not toxic. To that end, we used two cell lines in this study—one neuronal and one hepatic—because we would also need to assess whether antioxidants caused liver damage, which is our main sensor of toxicity,” says Fernanda Borges.
After several attempts, the part that gave the “best results” turned out to be an isoquinoline-derived cation.
“We were able to obtain an antioxidant that penetrates the mitochondria but does not cause toxic damage,” the researchers add, noting that this antioxidant has a “neuroprotective effect on cells.”
As part of the Pessoa Foundation for Science and Technology (FCT) program, researchers in partnership with the University of Montpellier (France) will test the effectiveness of these antioxidants in in vivo models.
The study, which is the result of more than 10 years of research aimed at developing new antioxidants, was carried out in collaboration with researchers from the Faculty of Pharmacy of the University of Porto, the Center for Neurology and Cell Biology of the University of Coimbra. and University of Santiago de Compostela, Spain.
Author: Portuguese
Source: CM Jornal
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