Novel Insights on CAI–CORM Hybrids: Evaluation of the CO Releasing Properties and Pain-Relieving Activity of Differently Substituted Coumarins for the Treatment of Rheumatoid Arthritis

Pain control is among the most important healthcare services
in
patients affected by rheumatoid arthritis (RA), but the current therapeutic
options (i.e., disease-modifying anti-rheumatic drugs) are limited
by the risk of the side effects. In this context, we proposed an innovative
approach based on the hybridization between carbonic anhydrase inhibitors
(CAIs) and CO releasing molecules (CORMs). The resulting CAI–CORM
hybrids were revealed to possess strong anti-inflammatory effects
in in vitro models of diseases and to relieve ache symptoms in an
in vivo RA rat model. In this work, we have deepened the study of
these promising hybrids, designing a library of coumarin-based compounds,
also including internal dicobalt hexacarbonyl systems. The results
obtained from the CO releasing study, the CA inhibitory activity,
and the in vivo pain-relief efficacy evaluation in the RA rat model
confirmed the success of this strategy, allowing us to consider CAI–CORM
hybrids promising anti-nociceptive agents against arthritis.