The progress of science and technology in the pharmaceutical industry has facilitated access to effective treatments. However, this has also led to a strong dependence on certain medications, often without fully considering their side effects.
For example, ibuprofen is one of the most widely used and well-known medications in Chile. According to data from the Institute of Public Health (ISP), between January and October 2021 alone, more than 4.7 million units were sold, placing it third in the ranking of best-selling drugs nationwide. Other commonly used anti-inflammatory drugs include naproxen, mefenamic acid, ketoprofen, and ketorolac.
This massive consumption reflects the Chilean population's strong dependence on anti-inflammatory drugs, despite scientific evidence warning of their adverse effects, such as gastric or renal damage when used for prolonged periods, thus prompting the need to seek effective and less harmful options for the body.
This is the view of Dr. Carolina Mascayano, an academic and researcher at the Faculty of Chemistry and Biology at Usach, who is leading a Fondecyt Regular project aimed at developing a new generation of compounds with anti-inflammatory potential. The goal is to find safer and more effective alternatives to current medications, capable of relieving inflammation without causing the adverse effects that currently limit the prolonged use of these drugs.
Fewer Side Effects
"We began by researching 5-LOX inhibitors from flavonoids, but we soon saw the need to go further and also address COX-2. This evolution led us to propose dual compounds that integrate both inflammatory pathways, paving the way for more comprehensive therapies with fewer side effects," says the researcher.
In other words, the research stems from studying traditional anti-inflammatory drugs and evolving toward the design of compounds that act on two enzymes relevant to the creation of a drug. The first is COX-2, responsible for producing prostaglandins that cause pain, fever, and inflammation. The second is 5-LOX, linked to the synthesis of leukotrienes, molecules that also participate in inflammatory processes and respiratory diseases. By focusing on both at the same time, more comprehensive treatments with fewer side effects than current drugs can be developed.
One of the project's innovative proposals is the incorporation of ferrocene, an organometallic compound that has gained prominence in medicinal chemistry in recent years. Its high stability, structural similarity to the phenolic ring common in many drugs, and low toxicity in animal models make it a particularly attractive fragment for drug design.
“By adding ferrocene to our molecules, we make them more effective and, at the same time, safer. This organometallic fragment enhances the action against inflammatory enzymes and opens up the possibility of developing treatments with fewer side effects than traditional anti-inflammatories,” explains Dr. Mascayano.
Impactful Interdisciplinary Research
Although this is pioneering basic science research, the project involves strong collaboration between different areas of knowledge. It involves chemists dedicated to the synthesis of new molecules, biochemists who perform biological tests, bioinformatics specialists who model the behavior of compounds on computers, as well as undergraduate, master's, and doctoral students who are involved in each stage.
"We work simultaneously on three core fronts: compound synthesis, biological testing, and computational studies," says Dr. Mascayano. She underscores the importance of teamwork, adding that "none of this would be possible without collaboration between different disciplines and the essential contribution of undergraduate and graduate students.
"Added to this effort is the collaboration with academics from the Faculty of Medical Sciences at Usach, which allows us to broaden our view to applications related to more complex pathologies, such as cancer. This joint work between chemistry, biology, and medicine makes the project an example of interdisciplinary research with great potential for impact.
“The integration with Medical Sciences enables us to project the work beyond inflammation and think about how these compounds could contribute to the treatment of diseases where COX-2 and 5-LOX play a key role, such as cancer,” concludes the researcher.