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Antioxidant Properties and Aldehyde Reactivity of PD-L1 Targeted Aryl-Pyrazolone Anticancer Agents
Small molecules targeting the PD-1/PD-L1 checkpoint are actively searched to complement the anticancer arsenal. Different molecular scaffolds have been reported, including phenyl-pyrazolone derivatives which potently inhibit binding of PD-L1 to PD-1. These molecules are structurally close to antioxi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143004/ https://www.ncbi.nlm.nih.gov/pubmed/35630791 http://dx.doi.org/10.3390/molecules27103316 |
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author | Leleu-Chavain, Natascha Regnault, Romain Ahouari, Hania Le Biannic, Raphaël Kouach, Mostafa Klupsch, Frédérique Magnez, Romain Vezin, Hervé Thuru, Xavier Bailly, Christian Goossens, Jean-François Millet, Régis |
author_facet | Leleu-Chavain, Natascha Regnault, Romain Ahouari, Hania Le Biannic, Raphaël Kouach, Mostafa Klupsch, Frédérique Magnez, Romain Vezin, Hervé Thuru, Xavier Bailly, Christian Goossens, Jean-François Millet, Régis |
author_sort | Leleu-Chavain, Natascha |
collection | PubMed |
description | Small molecules targeting the PD-1/PD-L1 checkpoint are actively searched to complement the anticancer arsenal. Different molecular scaffolds have been reported, including phenyl-pyrazolone derivatives which potently inhibit binding of PD-L1 to PD-1. These molecules are structurally close to antioxidant drug edaravone (EDA) used to treat amyotrophic lateral sclerosis. For this reason, we investigated the capacity of five PD-L1-binding phenyl-pyrazolone compounds (1–5) to scavenge the formation of oxygen free radicals using electron spin resonance spectroscopy with DPPH/DMPO probes. In addition, the reactivity of the compounds toward the oxidized base 5-formyluracil (5fU) was assessed using chromatography coupled to mass spectrometry and photodiode array detectors. The data revealed that the phenyl-pyrazolone derivatives display antioxidant properties and exhibit a variable reactivity toward 5fU. Compound 2 with a N-dichlorophenyl-pyrazolone moiety cumulates the three properties, being a potent PD-L1 binder, a robust antioxidant and an aldehyde-reactive compound. On the opposite, the adamantane derivative 5 is a potent PD-L1 binding with a reduced antioxidant potential and no aldehyde reactivity. The nature of the substituent on the phenyl-pyrazolone core modulates the antioxidant capacity and reactivity toward aromatic aldehydes. The molecular signature of the compound can be adapted at will, to confer additional properties to these PD-L1 binders. |
format | Online Article Text |
id | pubmed-9143004 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91430042022-05-29 Antioxidant Properties and Aldehyde Reactivity of PD-L1 Targeted Aryl-Pyrazolone Anticancer Agents Leleu-Chavain, Natascha Regnault, Romain Ahouari, Hania Le Biannic, Raphaël Kouach, Mostafa Klupsch, Frédérique Magnez, Romain Vezin, Hervé Thuru, Xavier Bailly, Christian Goossens, Jean-François Millet, Régis Molecules Article Small molecules targeting the PD-1/PD-L1 checkpoint are actively searched to complement the anticancer arsenal. Different molecular scaffolds have been reported, including phenyl-pyrazolone derivatives which potently inhibit binding of PD-L1 to PD-1. These molecules are structurally close to antioxidant drug edaravone (EDA) used to treat amyotrophic lateral sclerosis. For this reason, we investigated the capacity of five PD-L1-binding phenyl-pyrazolone compounds (1–5) to scavenge the formation of oxygen free radicals using electron spin resonance spectroscopy with DPPH/DMPO probes. In addition, the reactivity of the compounds toward the oxidized base 5-formyluracil (5fU) was assessed using chromatography coupled to mass spectrometry and photodiode array detectors. The data revealed that the phenyl-pyrazolone derivatives display antioxidant properties and exhibit a variable reactivity toward 5fU. Compound 2 with a N-dichlorophenyl-pyrazolone moiety cumulates the three properties, being a potent PD-L1 binder, a robust antioxidant and an aldehyde-reactive compound. On the opposite, the adamantane derivative 5 is a potent PD-L1 binding with a reduced antioxidant potential and no aldehyde reactivity. The nature of the substituent on the phenyl-pyrazolone core modulates the antioxidant capacity and reactivity toward aromatic aldehydes. The molecular signature of the compound can be adapted at will, to confer additional properties to these PD-L1 binders. MDPI 2022-05-21 /pmc/articles/PMC9143004/ /pubmed/35630791 http://dx.doi.org/10.3390/molecules27103316 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Leleu-Chavain, Natascha Regnault, Romain Ahouari, Hania Le Biannic, Raphaël Kouach, Mostafa Klupsch, Frédérique Magnez, Romain Vezin, Hervé Thuru, Xavier Bailly, Christian Goossens, Jean-François Millet, Régis Antioxidant Properties and Aldehyde Reactivity of PD-L1 Targeted Aryl-Pyrazolone Anticancer Agents |
title | Antioxidant Properties and Aldehyde Reactivity of PD-L1 Targeted Aryl-Pyrazolone Anticancer Agents |
title_full | Antioxidant Properties and Aldehyde Reactivity of PD-L1 Targeted Aryl-Pyrazolone Anticancer Agents |
title_fullStr | Antioxidant Properties and Aldehyde Reactivity of PD-L1 Targeted Aryl-Pyrazolone Anticancer Agents |
title_full_unstemmed | Antioxidant Properties and Aldehyde Reactivity of PD-L1 Targeted Aryl-Pyrazolone Anticancer Agents |
title_short | Antioxidant Properties and Aldehyde Reactivity of PD-L1 Targeted Aryl-Pyrazolone Anticancer Agents |
title_sort | antioxidant properties and aldehyde reactivity of pd-l1 targeted aryl-pyrazolone anticancer agents |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143004/ https://www.ncbi.nlm.nih.gov/pubmed/35630791 http://dx.doi.org/10.3390/molecules27103316 |
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