Maria J. Matos
“Nothing in life is to be feared; it is only to be understood.” Marie Curie
Research Projects
From small molecules to targeted therapies
Targeted therapies as a promising approach for neurodegenerative diseases
As the global population ages, neurodegenerative diseases are becoming more prevalent, posing significant challenges to public health. The 20th century saw a major demographic shift in industrialized countries, with similar trends now emerging in developing nations as life expectancy increases. This shift underscores the urgent need for effective treatments.
Research into the molecular mechanisms underlying these widespread diseases has fueled efforts to develop targeted therapies. By focusing on specific proteins involved in disease progression, we aim to create drugs that are not only more effective but also less toxic than traditional treatments. Targeted drug delivery, in particular, holds great promise, but there are still hurdles to overcome in order to achieve optimal clinical outcomes.
One of the primary challenges in drug development is ensuring that therapeutic agents reach their intended target at the right concentrations. Factors such as rapid renal clearance, degradation, and non-specific distribution complicate the delivery process. This is particularly true when attempting to deliver drugs to the central nervous system (CNS), which is protected by the blood-brain barrier (BBB).
To overcome this barrier, researchers are exploring innovative delivery methods that leverage the body’s natural transport systems. One promising approach is adsorptive-mediated endocytosis (AME), a mechanism that uses electrostatic interactions to facilitate the transport of positively charged substances across the BBB. By harnessing existing carrier proteins responsible for nutrient transport, AME-based delivery systems offer the potential to increase drug availability in the brain, opening new avenues for treatment.
Design, synthesis and pharmacological study of small molecules as potential drug candidates
In recent years, molecular hybridization has emerged as a promising strategy in drug discovery. This approach involves combining two or more pharmacophores (or parts of them) into a single molecule to create hybrid multifunctional compounds. By merging different biological activities, these hybrid molecules can enhance several key properties, such as modulating selectivity profiles, combining distinct or complementary mechanisms of action, and reducing side effects. Additionally, these molecules can be further optimized to improve pharmacokinetics and oral bioavailability.
Our research group specializes in designing and synthesizing hybrid compounds with a variety of bioactive chemical scaffolds, including coumarins, stilbenes (like resveratrol), benzofurans, thiophenes, carboxamides, chalcones, benzothiazoles, etc. To date, we have synthesized over 1,000 compounds, many of which show promising biological activities targeting various diseases, including neurodegenerative disorders, cardiovascular diseases, and neglected diseases like Chagas and malaria.
Among these compounds, arylcoumarins stand out due to their synthetic versatility and significant pharmacological potential. Coumarin-resveratrol hybrids were designed specifically for their multitarget properties, an approach that is increasingly explored for treating complex, multifactorial diseases like neurodegenerative conditions.