Bifunctional Sildenafil Diazeniumdiolates Acting as Phosphodiesterase 5 Inhibitors and Nitric Oxide Donors- Towards Wound Healing
© 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH..
Inefficient wound healing poses a global health challenge with a lack of efficient treatments. Wound healing issues often correlate with low endogenous nitric oxide (NO) levels. While exogenous delivery with NO-releasing compounds represents a promising therapeutic strategy, controlling the release of the highly reactive NO remains challenging. Phosphodiesterase 5 (PDE5) inhibitors, like sildenafil, have also been shown to promote wound healing. This study explores hybrid compounds, combining NO-releasing diazeniumdiolates with a sildenafil-derived PDE5 inhibitor. One compound demonstrated a favorable NO-release profile, triggered by an esterase (prodrug), and displayed in vitro nanomolar inhibition potency against PDE5 and thrombin-induced platelet aggregation. Both factors are known to promote blood flow and oxygenation. Thus, our findings unveil promising prospects for effective wound healing treatments.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
Chembiochem : a European journal of chemical biology - 25(2024), 8 vom: 16. Apr., Seite e202300801 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mas-Roselló, Josep [VerfasserIn] |
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| Links: |
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| Themen: |
31C4KY9ESH |
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| Anmerkungen: |
Date Completed 18.04.2024 Date Revised 18.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/cbic.202300801 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM369204336 |
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| 520 | |a Inefficient wound healing poses a global health challenge with a lack of efficient treatments. Wound healing issues often correlate with low endogenous nitric oxide (NO) levels. While exogenous delivery with NO-releasing compounds represents a promising therapeutic strategy, controlling the release of the highly reactive NO remains challenging. Phosphodiesterase 5 (PDE5) inhibitors, like sildenafil, have also been shown to promote wound healing. This study explores hybrid compounds, combining NO-releasing diazeniumdiolates with a sildenafil-derived PDE5 inhibitor. One compound demonstrated a favorable NO-release profile, triggered by an esterase (prodrug), and displayed in vitro nanomolar inhibition potency against PDE5 and thrombin-induced platelet aggregation. Both factors are known to promote blood flow and oxygenation. Thus, our findings unveil promising prospects for effective wound healing treatments | ||
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