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.

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 / Berrino, Emanuela; Micheli, Laura; Carradori, Simone; di Cesare Mannelli, Lorenzo; Guglielmi, Paolo; De Luca, Alessandro; Carta, Fabrizio; Ghelardini, Carla; Secci, Daniela; Supuran, Claudiu T.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - (2023). [10.1021/acs.jmedchem.2c01706]

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 Berrino;Laura Micheli;Simone Carradori;Paolo Guglielmi;Daniela Secci;Claudiu T. Supuran
2023

Abstract

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.
2023
Carbonic Anhydrase Inhibitors; CORMs; CO release; Rheumatoid Arthritis; Pain
01 Pubblicazione su rivista::01a Articolo in rivista
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 / Berrino, Emanuela; Micheli, Laura; Carradori, Simone; di Cesare Mannelli, Lorenzo; Guglielmi, Paolo; De Luca, Alessandro; Carta, Fabrizio; Ghelardini, Carla; Secci, Daniela; Supuran, Claudiu T.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - (2023). [10.1021/acs.jmedchem.2c01706]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1666710
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