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 ca...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/11/1363 |
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| author | José M. Alonso Alejandro Escobar-Peso Israel Fernández Alberto Alcázar José Marco-Contelles |
| author_facet | José M. Alonso Alejandro Escobar-Peso Israel Fernández Alberto Alcázar José Marco-Contelles |
| author_sort | José M. Alonso |
| collection | DOAJ |
| 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, QN4 and 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. |
| first_indexed | 2024-03-09T18:44:58Z |
| format | Article |
| id | doaj.art-57e9af1f94d34c99a91887172af4e606 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T18:44:58Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-57e9af1f94d34c99a91887172af4e6062023-11-24T06:18:44ZengMDPI AGPharmaceuticals1424-82472022-11-011511136310.3390/ph15111363Improving the Efficacy of Quinolylnitrones for Ischemic Stroke Therapy, QN4 and QN15 as New Neuroprotective Agents after Oxygen–Glucose Deprivation/Reoxygenation-Induced Neuronal InjuryJosé M. Alonso0Alejandro Escobar-Peso1Israel Fernández2Alberto Alcázar3José Marco-Contelles4Laboratory of Medicinal Chemistry (IQOG, CSIC), C/Juan de la Cierva 3, 28006 Madrid, SpainDepartment of Research, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. Colmenar km 9.1, 28034 Madrid, SpainDepartamento de Química Orgánica I and Centro de Innovación en Química Avanzada (ORFEO-CINQA), Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartment of Research, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. Colmenar km 9.1, 28034 Madrid, SpainLaboratory of Medicinal Chemistry (IQOG, CSIC), C/Juan de la Cierva 3, 28006 Madrid, SpainIn 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, QN4 and 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.https://www.mdpi.com/1424-8247/15/11/1363brain ischemiaDFT calculationsischemic strokeneuroprotectionnitronesquinolylnitrones |
| spellingShingle | José M. Alonso Alejandro Escobar-Peso Israel Fernández Alberto Alcázar José Marco-Contelles Improving the Efficacy of Quinolylnitrones for Ischemic Stroke Therapy, QN4 and QN15 as New Neuroprotective Agents after Oxygen–Glucose Deprivation/Reoxygenation-Induced Neuronal Injury Pharmaceuticals brain ischemia DFT calculations ischemic stroke neuroprotection nitrones quinolylnitrones |
| 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 |
| 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_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_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 |
| topic | brain ischemia DFT calculations ischemic stroke neuroprotection nitrones quinolylnitrones |
| url | https://www.mdpi.com/1424-8247/15/11/1363 |
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