Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by inflammation of the synovial tissue in joints, joint destruction, pain and incapacity. RA strongly diminishes the patients? capabilities to perform easy daily activities. RA carries an extraordinary economic impact. In Portugal the annual costs with RA are 119.525.000 €.
The recent progresses made in the RA treatment are undeniable, especially after the introduction of biologic drugs as alternatives to the conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs). However, treatments have low efficacy, are extremely expensive, and are flawed by potentially hazardous side effects. All these facts reason the sustained and urgent need to find effective and more affordable therapies to modulate RA and return to patients the desired quality of life.
2-Styrylchromones (2-SC) are able to regulate the immune response, mainly due to their ability to inhibit different steps of the inflammatory process cascade. Despite their known anti-inflammatory potential there is hardly any study in the literature about their potential application as therapeutic drugs in RA. In this sense, this project proposes the development of a systematic and multitask work where the main aim is to synthesize a library of 2-SC and evaluate their potential as anti-RA drugs, in in vitro and in vivo models. To achieve this goal a team with two complementary and intimately related areas of expertise was built: organic synthesis and biological activity evaluation. Such interdisciplinary work will certainly guarantee the successful achievement of all the project stages.
Overall, this project comprise 3 linked and interdependent stages:
1. Synthesis of a complete panel of structurally related 2-SC, making structure adjustments according to the results obtained in the biologic assays;
2. In vitro testing of the selected panel of structurally related 2-SC in in vitro RA models;
3. Testing the activity of the most promising 2-SC in an in vivo model of RA, focusing not only in the anti-inflammatory activity, but also in the analgesic one.
At the final stage of this project, the most active(s) 2-SC found will be patented and considered as prototype for the design and development of new anti-RA agents.
This project will contribute to the finding of a 2-SC structure clearly effective in the modulation of inflammatory and pain conditions of RA. This kind of compound is envisioned as a more affordable therapy, however complying the ultimate aim, return to patients the quality of life lost during the development of RA.