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.
Emanuela BerrinoLaura MicheliSimone CarradoriLorenzo di Cesare MannelliPaolo GuglielmiAlessandro De LucaFabrizio CartaCarla GhelardiniDaniela SecciClaudiu T SupuranPublished in: Journal of medicinal chemistry (2023)
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.
Keyphrases
- rheumatoid arthritis
- disease activity
- healthcare
- chronic pain
- neuropathic pain
- ankylosing spondylitis
- pain management
- end stage renal disease
- interstitial lung disease
- mental health
- primary care
- chronic kidney disease
- spinal cord injury
- newly diagnosed
- ejection fraction
- peritoneal dialysis
- social media
- prognostic factors
- spinal cord
- systemic lupus erythematosus
- depressive symptoms
- systemic sclerosis
- fluorescent probe
- label free
- single molecule