A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes

• Main Authors: Federico Appetecchia (Author), Sara Consalvi (Author), Emanuela Berrino (Author), Marialucia Gallorini (Author), Arianna Granese (Author), Cristina Campestre (Author), Simone Carradori (Author), Mariangela Biava (Author), Giovanna Poce (Author)
• Format: Book
• Published: MDPI AG, 2021-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antiox10111828; 2076-3921
• Keywords: CO-releasing molecules; tenocytes; PGE₂; 1,5-diarylpyrrole; 1,5-diarylpyrazole; carbon monoxide; Therapeutics. Pharmacology; RM1-950
• Source: Antioxidants, Vol 10, Iss 11, p 1828 (2021)

Carbon monoxide (CO) can prevent cell and tissue damage by restoring redox homeostasis and counteracting inflammation. CO-releasing molecules (CORMs) can release a controlled amount of CO to cells and are emerging as a safer therapeutic alternative to delivery of CO in vivo. Sustained oxidative stress and inflammation can cause chronic pain and disability in tendon-related diseases, whose therapeutic management is still a challenge. In this light, we developed three small subsets of 1,5-diarylpyrrole and pyrazole dicobalt(0)hexacarbonyl (DCH)-CORMs to assess their potential use in musculoskeletal diseases. A myoglobin-based spectrophotometric assay showed that these CORMs act as slow and efficient CO-releasers. Five selected compounds were then tested on human primary-derived tenocytes before and after hydrogen peroxide stimulation to assess their efficacy in restoring cell redox homeostasis and counteracting inflammation in terms of PGE₂ secretion. The obtained results showed an improvement in tendon homeostasis and a cytoprotective effect, reflecting their activity as CO-releasers, and a reduction of PGE₂ secretion. As these compounds contain structural fragments of COX-2 selective inhibitors, we hypothesized that such a composite mechanism of action results from the combination of CO-release and COX-2 inhibition and that these compounds might have a potential role as dual-acting therapeutic agents in tendon-derived diseases.