Increasing scientific studies show that several diseases result from mitochondrial alterations, which in turn are caused by pathological oxidative stress. So, in this context, it seems simple that an effective therapeutic strategy is to target mitochondrial oxidative stress.
However, while the role of mitochondria in disease development is consensual, targeting to this organelle to prevent its pathogenic changes, is not always easily achievable.
Researchers from the Center for Neuroscience and Cell Biology (CNC) developed an antioxidant agent based on caffeic acid that works as a therapeutic solution for mitochondrial oxidative stress.
Phenolic compounds, such as caffeic acid, have peculiar properties regarding this scope (of mitochondrial oxidative stress). In addition to having antioxidant properties, some of those compounds target active molecules to mitochondria.
José Teixeira and his research group, from CNC of the University of Coimbra, conducted a research study aiming to develop a new therapeutic solution for pathologies related to mitochondrial oxidative stress. It involved the development of agents based on caffeic acid of natural origin that targeted mitochondria. Then, they biologically evaluated the compounds produced, by measuring physicochemical properties, antioxidant activity and biological toxicity in different in vitro models (isolated rat liver mitochondria and cell lines).
Some of the synthesized compounds proved to be potential candidates for the development of a drug candidate with therapeutic application in mitochondrial oxidative stress-related diseases. The results of this study also showed that chemical modulation of natural compounds is a strategy to attain valid innovative antioxidants without toxicity risks.
The authors concluded highlighting that “the present study is part of a drug discovery project to perform a lead optimization process, carried out by tailored structural modification on a lead compound in order to improve mitochondrial delivery and reduce toxicity. Accordingly, we used pre-clinical biological models such as isolated rat liver mitochondria and cell lines. This initial stage allowed us to select the more promising molecule to be used and validated in more robust animal models of disease.”
For now, these are the results of a promising study in the field of pathologies related to mitochondria oxidative stress, and certainly more great discoveries are coming.
Reference:
Teixeira, J, et. al (2019). Development of a mitochondriotropic antioxidant based on caffeic acid: proof of concept on cellular and mitochondrial oxidative stress models, J. Med. Chem., 62, 21, 9753–9771. DOI: https://doi.org/10.1021/acs.jmedchem.9b01196
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