Nitrostilbenes: Synthesis and Biological Evaluation as Potential Anti-Influenza Virus Agents
Resveratrol (RSV) is a natural stilbene polyphenolic compound found in several plant species. It is characterized by antioxidant properties, and its role in controlling viral replication has been demonstrated for different viral infections. Despite its promising antiviral properties, RSV biological...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/9/1061 |
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| author | Marta De Angelis Barbara De Filippis Marwa Balaha Letizia Giampietro Mariya Timotey Miteva Giovanna De Chiara Anna Teresa Palamara Lucia Nencioni Adriano Mollica |
| author_facet | Marta De Angelis Barbara De Filippis Marwa Balaha Letizia Giampietro Mariya Timotey Miteva Giovanna De Chiara Anna Teresa Palamara Lucia Nencioni Adriano Mollica |
| author_sort | Marta De Angelis |
| collection | DOAJ |
| description | Resveratrol (RSV) is a natural stilbene polyphenolic compound found in several plant species. It is characterized by antioxidant properties, and its role in controlling viral replication has been demonstrated for different viral infections. Despite its promising antiviral properties, RSV biological activity is limited by its low bioavailability and high metabolic rate. In this study, we optimized its structure by synthesizing new RSV derivatives that maintained the phenolic scaffold and contained different substitution patterns and evaluated their potential anti-influenza virus activity. The results showed that viral protein synthesis decreased 24 h post infection; particularly, the nitro-containing compounds strongly reduced viral replication. The molecules did not exert their antioxidant properties during infection; in fact, they were not able to rescue the virus-induced drop in GSH content or improve the antioxidant response mediated by the Nrf2 transcription factor and G6PD enzyme. Similar to what has already been reported for RSV, they interfered with the nuclear-cytoplasmic traffic of viral nucleoprotein, probably inhibiting cellular kinases involved in the regulation of specific steps of the virus life cycle. Overall, the data indicate that more lipophilic RSV derivatives have improved antiviral efficacy compared with RSV and open the way for new cell-targeted antiviral strategies. |
| first_indexed | 2024-03-09T22:52:01Z |
| format | Article |
| id | doaj.art-1cd08b7d123a42919396451ff8d50f66 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T22:52:01Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-1cd08b7d123a42919396451ff8d50f662023-11-23T18:17:51ZengMDPI AGPharmaceuticals1424-82472022-08-01159106110.3390/ph15091061Nitrostilbenes: Synthesis and Biological Evaluation as Potential Anti-Influenza Virus AgentsMarta De Angelis0Barbara De Filippis1Marwa Balaha2Letizia Giampietro3Mariya Timotey Miteva4Giovanna De Chiara5Anna Teresa Palamara6Lucia Nencioni7Adriano Mollica8Laboratory Affiliated to Institute, Department of Public Health and Infectious Diseases, Pasteur Italia-Cenci Bolognetti Foundation, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Pharmacy, University “G. d’Annunzio” University of Chieti-Pescara, via dei Vestini 31, 66100 Chieti, ItalyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafr El Sheikh 33516, EgyptDepartment of Pharmacy, University “G. d’Annunzio” University of Chieti-Pescara, via dei Vestini 31, 66100 Chieti, ItalyLaboratory Affiliated to Institute, Department of Public Health and Infectious Diseases, Pasteur Italia-Cenci Bolognetti Foundation, Sapienza University of Rome, 00185 Rome, ItalyInstitute of Translational Pharmacology, National Research Council, 00133 Rome, ItalyLaboratory Affiliated to Institute, Department of Public Health and Infectious Diseases, Pasteur Italia-Cenci Bolognetti Foundation, Sapienza University of Rome, 00185 Rome, ItalyLaboratory Affiliated to Institute, Department of Public Health and Infectious Diseases, Pasteur Italia-Cenci Bolognetti Foundation, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Pharmacy, University “G. d’Annunzio” University of Chieti-Pescara, via dei Vestini 31, 66100 Chieti, ItalyResveratrol (RSV) is a natural stilbene polyphenolic compound found in several plant species. It is characterized by antioxidant properties, and its role in controlling viral replication has been demonstrated for different viral infections. Despite its promising antiviral properties, RSV biological activity is limited by its low bioavailability and high metabolic rate. In this study, we optimized its structure by synthesizing new RSV derivatives that maintained the phenolic scaffold and contained different substitution patterns and evaluated their potential anti-influenza virus activity. The results showed that viral protein synthesis decreased 24 h post infection; particularly, the nitro-containing compounds strongly reduced viral replication. The molecules did not exert their antioxidant properties during infection; in fact, they were not able to rescue the virus-induced drop in GSH content or improve the antioxidant response mediated by the Nrf2 transcription factor and G6PD enzyme. Similar to what has already been reported for RSV, they interfered with the nuclear-cytoplasmic traffic of viral nucleoprotein, probably inhibiting cellular kinases involved in the regulation of specific steps of the virus life cycle. Overall, the data indicate that more lipophilic RSV derivatives have improved antiviral efficacy compared with RSV and open the way for new cell-targeted antiviral strategies.https://www.mdpi.com/1424-8247/15/9/1061resveratrolpolyphenolsinfluenza virusredox stateantivirals |
| spellingShingle | Marta De Angelis Barbara De Filippis Marwa Balaha Letizia Giampietro Mariya Timotey Miteva Giovanna De Chiara Anna Teresa Palamara Lucia Nencioni Adriano Mollica Nitrostilbenes: Synthesis and Biological Evaluation as Potential Anti-Influenza Virus Agents Pharmaceuticals resveratrol polyphenols influenza virus redox state antivirals |
| title | Nitrostilbenes: Synthesis and Biological Evaluation as Potential Anti-Influenza Virus Agents |
| title_full | Nitrostilbenes: Synthesis and Biological Evaluation as Potential Anti-Influenza Virus Agents |
| title_fullStr | Nitrostilbenes: Synthesis and Biological Evaluation as Potential Anti-Influenza Virus Agents |
| title_full_unstemmed | Nitrostilbenes: Synthesis and Biological Evaluation as Potential Anti-Influenza Virus Agents |
| title_short | Nitrostilbenes: Synthesis and Biological Evaluation as Potential Anti-Influenza Virus Agents |
| title_sort | nitrostilbenes synthesis and biological evaluation as potential anti influenza virus agents |
| topic | resveratrol polyphenols influenza virus redox state antivirals |
| url | https://www.mdpi.com/1424-8247/15/9/1061 |
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