Ricerc@Sapienza

Rheumatoid Arthritis (RA) is a chronic and systemic autoimmune disease which primary affect the lining of the joints, inducing ache symptoms deeply impacting life quality of the patients. Moreover, the chronic inflammation typical of RA has been related with higher cancer incidence. Currently RA pharmacological treatments include drugs acting to slow or stop the course of the disease and those acting to ease the symptoms. However, despite recent progresses in RA treatment there is still no effective cure. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most used drugs to control the symptoms of RA although their prolonged use is highly hampered by gastric and cardiovascular toxicity issues. Association of NSAIDs with therapeutic agents able to mitigate their adverse effects, also contributing to their anti-inflammatory activity would be of great interest for the global community. By exploiting the ¿hybridization approach¿, this project aims to combine the anti-inflammatory action of NSAIDs with the gastro- and cardio-protective activities of Carbon Monoxide (CO), released in a controlled manner by a metallo-organic scaffold properly installed on the Oxicam nucleous. Cobalt and Manganese containing CO-RM/NSAID hybrids will be designed, synthetized and assayed for their CO releasing properties, by means of the widely used Myoglobin carbonylation assay, available in-house. The anti-inflammatory and pain relieving activities will be evaluated in both in vitro and in vivo models of RA. By using a ratiometric fluorescent probe, the CO release from CO-RM/NSAID will be assayed also in the cellular medium. The availability of solid preliminary data, the well-established synthetic and analytical methodologies, and the translational character of the proposal, make this project feasible and appealing for a large scientific community, allowing to gain more insights in inflammation-related diseases treatment.