A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes
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 stre...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/11/1828 |
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| author | Federico Appetecchia Sara Consalvi Emanuela Berrino Marialucia Gallorini Arianna Granese Cristina Campestre Simone Carradori Mariangela Biava Giovanna Poce |
| author_facet | Federico Appetecchia Sara Consalvi Emanuela Berrino Marialucia Gallorini Arianna Granese Cristina Campestre Simone Carradori Mariangela Biava Giovanna Poce |
| author_sort | Federico Appetecchia |
| collection | DOAJ |
| description | 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 PGE<sub>2</sub> secretion. The obtained results showed an improvement in tendon homeostasis and a cytoprotective effect, reflecting their activity as CO-releasers, and a reduction of PGE<sub>2</sub> 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. |
| first_indexed | 2024-03-10T05:45:27Z |
| format | Article |
| id | doaj.art-b2ff742f5df44003bbfc475b14a2710c |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T05:45:27Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-b2ff742f5df44003bbfc475b14a2710c2023-11-22T22:14:18ZengMDPI AGAntioxidants2076-39212021-11-011011182810.3390/antiox10111828A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary TenocytesFederico Appetecchia0Sara Consalvi1Emanuela Berrino2Marialucia Gallorini3Arianna Granese4Cristina Campestre5Simone Carradori6Mariangela Biava7Giovanna Poce8Department of Chemistry and Technologies of Drug, Sapienza University of Rome, piazzale A. Moro 5, 00185 Rome, ItalyDepartment of Chemistry and Technologies of Drug, Sapienza University of Rome, piazzale A. Moro 5, 00185 Rome, ItalyDepartment of Chemistry and Technologies of Drug, Sapienza University of Rome, piazzale A. Moro 5, 00185 Rome, ItalyDepartment of Pharmacy, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, ItalyDepartment of Chemistry and Technologies of Drug, Sapienza University of Rome, piazzale A. Moro 5, 00185 Rome, ItalyDepartment of Pharmacy, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, ItalyDepartment of Pharmacy, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, ItalyDepartment of Chemistry and Technologies of Drug, Sapienza University of Rome, piazzale A. Moro 5, 00185 Rome, ItalyDepartment of Chemistry and Technologies of Drug, Sapienza University of Rome, piazzale A. Moro 5, 00185 Rome, ItalyCarbon 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 PGE<sub>2</sub> secretion. The obtained results showed an improvement in tendon homeostasis and a cytoprotective effect, reflecting their activity as CO-releasers, and a reduction of PGE<sub>2</sub> 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.https://www.mdpi.com/2076-3921/10/11/1828CO-releasing moleculestenocytesPGE<sub>2</sub>1,5-diarylpyrrole1,5-diarylpyrazolecarbon monoxide |
| spellingShingle | Federico Appetecchia Sara Consalvi Emanuela Berrino Marialucia Gallorini Arianna Granese Cristina Campestre Simone Carradori Mariangela Biava Giovanna Poce A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes Antioxidants CO-releasing molecules tenocytes PGE<sub>2</sub> 1,5-diarylpyrrole 1,5-diarylpyrazole carbon monoxide |
| title | A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes |
| title_full | A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes |
| title_fullStr | A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes |
| title_full_unstemmed | A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes |
| title_short | A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes |
| title_sort | novel class of dual acting dch corms counteracts oxidative stress induced inflammation in human primary tenocytes |
| topic | CO-releasing molecules tenocytes PGE<sub>2</sub> 1,5-diarylpyrrole 1,5-diarylpyrazole carbon monoxide |
| url | https://www.mdpi.com/2076-3921/10/11/1828 |
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