Improving the Efficacy of Quinolylnitrones for Ischemic Stroke Therapy, QN4 and QN15 as New Neuroprotective Agents after Oxygen–Glucose Deprivation/Reoxygenation-Induced Neuronal Injury

In our search for new neuroprotective agents for stroke therapy to improve the pharmacological profile of the compound quinolylnitrone QN23, we have prepared and studied sixteen new related and easily available quinolylnitrones. As a result, we have identified compounds QN4 and QN15 as promising can...

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Authors: Fernández López, Israel, Alonso Gómez, José Miguel, Escobar Peso, Alejandro, Alcázar, Alberto, Marco Contelles, José
Format: article
Publication Date:2022
Country:España
Institution:Universidad Complutense de Madrid (UCM)
Repository:Docta Complutense
Language:English
OAI Identifier:oai:docta.ucm.es:20.500.14352/88175
Online Access:https://hdl.handle.net/20.500.14352/88175
Access Level:Open access
Keyword:547
Ischemia
DFT calculations
Ischemic stroke
Neuroprotection
Nitrones
Quinolylnitrones
Imultipotent antioxidant drugs
Química orgánica (Química)
2306 Química Orgánica
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oai_identifier_str oai:docta.ucm.es:20.500.14352/88175
network_acronym_str ES
network_name_str España
repository_id_str
spelling Improving the Efficacy of Quinolylnitrones for Ischemic Stroke Therapy, QN4 and QN15 as New Neuroprotective Agents after Oxygen–Glucose Deprivation/Reoxygenation-Induced Neuronal InjuryFernández López, IsraelAlonso Gómez, José MiguelEscobar Peso, AlejandroAlcázar, AlbertoMarco Contelles, José547IschemiaDFT calculationsIschemic strokeNeuroprotectionNitronesQuinolylnitronesImultipotent antioxidant drugsQuímica orgánica (Química)2306 Química OrgánicaIn our search for new neuroprotective agents for stroke therapy to improve the pharmacological profile of the compound quinolylnitrone QN23, we have prepared and studied sixteen new related and easily available quinolylnitrones. As a result, we have identified compounds QN4 and QN15 as promising candidates showing high neuroprotection power in a cellular experimental model of ischemia. Even though they were found to be less active than our current lead compound QN23,QN4 and QN15 provide an improved potency and, particularly for QN4, an expanded range of tolerability and improved solubility compared to the parent compound. A computational DFT-based analysis has been carried out to understand the antioxidant power of quinolylnitrones QN23, QN4and QN15. Altogether, these results show that subtle, simple modifications of the quinolylnitrone scaffold are tolerated, providing high neuroprotective activity and optimization of the pharmacological potency required for an improved design and future drug developments in the field.MDPIUniversidad Complutense de Madrid20222022-11-0720222022-11-07journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/88175reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/881752026-06-02T12:44:21Z
dc.title.none.fl_str_mv Improving the Efficacy of Quinolylnitrones for Ischemic Stroke Therapy, QN4 and QN15 as New Neuroprotective Agents after Oxygen–Glucose Deprivation/Reoxygenation-Induced Neuronal Injury
title Improving the Efficacy of Quinolylnitrones for Ischemic Stroke Therapy, QN4 and QN15 as New Neuroprotective Agents after Oxygen–Glucose Deprivation/Reoxygenation-Induced Neuronal Injury
spellingShingle Improving the Efficacy of Quinolylnitrones for Ischemic Stroke Therapy, QN4 and QN15 as New Neuroprotective Agents after Oxygen–Glucose Deprivation/Reoxygenation-Induced Neuronal Injury
Fernández López, Israel
547
Ischemia
DFT calculations
Ischemic stroke
Neuroprotection
Nitrones
Quinolylnitrones
Imultipotent antioxidant drugs
Química orgánica (Química)
2306 Química Orgánica
title_short Improving the Efficacy of Quinolylnitrones for Ischemic Stroke Therapy, QN4 and QN15 as New Neuroprotective Agents after Oxygen–Glucose Deprivation/Reoxygenation-Induced Neuronal Injury
title_full Improving the Efficacy of Quinolylnitrones for Ischemic Stroke Therapy, QN4 and QN15 as New Neuroprotective Agents after Oxygen–Glucose Deprivation/Reoxygenation-Induced Neuronal Injury
title_fullStr Improving the Efficacy of Quinolylnitrones for Ischemic Stroke Therapy, QN4 and QN15 as New Neuroprotective Agents after Oxygen–Glucose Deprivation/Reoxygenation-Induced Neuronal Injury
title_full_unstemmed Improving the Efficacy of Quinolylnitrones for Ischemic Stroke Therapy, QN4 and QN15 as New Neuroprotective Agents after Oxygen–Glucose Deprivation/Reoxygenation-Induced Neuronal Injury
title_sort Improving the Efficacy of Quinolylnitrones for Ischemic Stroke Therapy, QN4 and QN15 as New Neuroprotective Agents after Oxygen–Glucose Deprivation/Reoxygenation-Induced Neuronal Injury
dc.creator.none.fl_str_mv Fernández López, Israel
Alonso Gómez, José Miguel
Escobar Peso, Alejandro
Alcázar, Alberto
Marco Contelles, José
author Fernández López, Israel
author_facet Fernández López, Israel
Alonso Gómez, José Miguel
Escobar Peso, Alejandro
Alcázar, Alberto
Marco Contelles, José
author_role author
author2 Alonso Gómez, José Miguel
Escobar Peso, Alejandro
Alcázar, Alberto
Marco Contelles, José
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 547
Ischemia
DFT calculations
Ischemic stroke
Neuroprotection
Nitrones
Quinolylnitrones
Imultipotent antioxidant drugs
Química orgánica (Química)
2306 Química Orgánica
topic 547
Ischemia
DFT calculations
Ischemic stroke
Neuroprotection
Nitrones
Quinolylnitrones
Imultipotent antioxidant drugs
Química orgánica (Química)
2306 Química Orgánica
description In our search for new neuroprotective agents for stroke therapy to improve the pharmacological profile of the compound quinolylnitrone QN23, we have prepared and studied sixteen new related and easily available quinolylnitrones. As a result, we have identified compounds QN4 and QN15 as promising candidates showing high neuroprotection power in a cellular experimental model of ischemia. Even though they were found to be less active than our current lead compound QN23,QN4 and QN15 provide an improved potency and, particularly for QN4, an expanded range of tolerability and improved solubility compared to the parent compound. A computational DFT-based analysis has been carried out to understand the antioxidant power of quinolylnitrones QN23, QN4and QN15. Altogether, these results show that subtle, simple modifications of the quinolylnitrone scaffold are tolerated, providing high neuroprotective activity and optimization of the pharmacological potency required for an improved design and future drug developments in the field.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-11-07
2022
2022-11-07
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/88175
url https://hdl.handle.net/20.500.14352/88175
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869406422879436801
score 15,301603

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