Preclinical Characterization of Antioxidant Quinolyl Nitrone QN23 as a New Candidate for the Treatment of Ischemic Stroke
Nitrones are encouraging drug candidates for the treatment of oxidative stress-driven diseases such as acute ischemic stroke (AIS). In a previous study, we found a promising quinolylnitrone, QN23, which exerted a neuroprotective effect in neuronal cell cultures subjected to oxygen–glucose deprivatio...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/6/1186 |
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| author | Emma Martínez-Alonso Alejandro Escobar-Peso Alicia Aliena-Valero Germán Torregrosa Mourad Chioua Rocío Fernández-Serra Daniel González-Nieto Youness Ouahid Juan B. Salom Jaime Masjuan José Marco-Contelles Alberto Alcázar |
| author_facet | Emma Martínez-Alonso Alejandro Escobar-Peso Alicia Aliena-Valero Germán Torregrosa Mourad Chioua Rocío Fernández-Serra Daniel González-Nieto Youness Ouahid Juan B. Salom Jaime Masjuan José Marco-Contelles Alberto Alcázar |
| author_sort | Emma Martínez-Alonso |
| collection | DOAJ |
| description | Nitrones are encouraging drug candidates for the treatment of oxidative stress-driven diseases such as acute ischemic stroke (AIS). In a previous study, we found a promising quinolylnitrone, QN23, which exerted a neuroprotective effect in neuronal cell cultures subjected to oxygen–glucose deprivation and in experimental models of cerebral ischemia. In this paper, we update the biological and pharmacological characterization of QN23. We describe the suitability of intravenous administration of QN23 to induce neuroprotection in transitory four-vessel occlusion (4VO) and middle cerebral artery occlusion (tMCAO) experimental models of brain ischemia by assessing neuronal death, apoptosis induction, and infarct area, as well as neurofunctional outcomes. QN23 significantly decreased the neuronal death and apoptosis induced by the ischemic episode in a dose-dependent manner and showed a therapeutic effect when administered up to 3 h after post-ischemic reperfusion onset, effects that remained 11 weeks after the ischemic episode. In addition, QN23 significantly reduced infarct volume, thus recovering the motor function in a tMCAO model. Remarkably, we assessed the antioxidant activity of QN23 in vivo using dihydroethidium as a molecular probe for radical species. Finally, we describe QN23 pharmacokinetic parameters. All these results pointing to QN23 as an interesting and promising preclinical candidate for the treatment of AIS. |
| first_indexed | 2024-03-10T00:33:23Z |
| format | Article |
| id | doaj.art-5d0ddac6fefa4f3ebcbbfac8601dd46c |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T00:33:23Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-5d0ddac6fefa4f3ebcbbfac8601dd46c2023-11-23T15:21:03ZengMDPI AGAntioxidants2076-39212022-06-01116118610.3390/antiox11061186Preclinical Characterization of Antioxidant Quinolyl Nitrone QN23 as a New Candidate for the Treatment of Ischemic StrokeEmma Martínez-Alonso0Alejandro Escobar-Peso1Alicia Aliena-Valero2Germán Torregrosa3Mourad Chioua4Rocío Fernández-Serra5Daniel González-Nieto6Youness Ouahid7Juan B. Salom8Jaime Masjuan9José Marco-Contelles10Alberto Alcázar11Department of Research, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, SpainDepartment of Research, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, SpainUnidad Mixta de Investigación Cerebrovascular, Instituto de Investigación Sanitaria La Fe, Universidad de Valencia, 46026 Valencia, SpainUnidad Mixta de Investigación Cerebrovascular, Instituto de Investigación Sanitaria La Fe, Universidad de Valencia, 46026 Valencia, SpainLaboratory of Medicinal Chemistry (IQOG, CSIC), 28006 Madrid, SpainCenter for Biomedical Technology, Universidad Politécnica de Madrid, 28223 Pozuelo de Alarcón, SpainCenter for Biomedical Technology, Universidad Politécnica de Madrid, 28223 Pozuelo de Alarcón, SpainIsquaemia Biotech SL, 28102 Alcobendas, SpainUnidad Mixta de Investigación Cerebrovascular, Instituto de Investigación Sanitaria La Fe, Universidad de Valencia, 46026 Valencia, SpainDepartment of Neurology, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, SpainLaboratory of Medicinal Chemistry (IQOG, CSIC), 28006 Madrid, SpainDepartment of Research, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, SpainNitrones are encouraging drug candidates for the treatment of oxidative stress-driven diseases such as acute ischemic stroke (AIS). In a previous study, we found a promising quinolylnitrone, QN23, which exerted a neuroprotective effect in neuronal cell cultures subjected to oxygen–glucose deprivation and in experimental models of cerebral ischemia. In this paper, we update the biological and pharmacological characterization of QN23. We describe the suitability of intravenous administration of QN23 to induce neuroprotection in transitory four-vessel occlusion (4VO) and middle cerebral artery occlusion (tMCAO) experimental models of brain ischemia by assessing neuronal death, apoptosis induction, and infarct area, as well as neurofunctional outcomes. QN23 significantly decreased the neuronal death and apoptosis induced by the ischemic episode in a dose-dependent manner and showed a therapeutic effect when administered up to 3 h after post-ischemic reperfusion onset, effects that remained 11 weeks after the ischemic episode. In addition, QN23 significantly reduced infarct volume, thus recovering the motor function in a tMCAO model. Remarkably, we assessed the antioxidant activity of QN23 in vivo using dihydroethidium as a molecular probe for radical species. Finally, we describe QN23 pharmacokinetic parameters. All these results pointing to QN23 as an interesting and promising preclinical candidate for the treatment of AIS.https://www.mdpi.com/2076-3921/11/6/1186antioxidantsbrain ischemiaischemic strokeneuroprotectionquinolyl nitronespharmacokinetics |
| spellingShingle | Emma Martínez-Alonso Alejandro Escobar-Peso Alicia Aliena-Valero Germán Torregrosa Mourad Chioua Rocío Fernández-Serra Daniel González-Nieto Youness Ouahid Juan B. Salom Jaime Masjuan José Marco-Contelles Alberto Alcázar Preclinical Characterization of Antioxidant Quinolyl Nitrone QN23 as a New Candidate for the Treatment of Ischemic Stroke Antioxidants antioxidants brain ischemia ischemic stroke neuroprotection quinolyl nitrones pharmacokinetics |
| title | Preclinical Characterization of Antioxidant Quinolyl Nitrone QN23 as a New Candidate for the Treatment of Ischemic Stroke |
| title_full | Preclinical Characterization of Antioxidant Quinolyl Nitrone QN23 as a New Candidate for the Treatment of Ischemic Stroke |
| title_fullStr | Preclinical Characterization of Antioxidant Quinolyl Nitrone QN23 as a New Candidate for the Treatment of Ischemic Stroke |
| title_full_unstemmed | Preclinical Characterization of Antioxidant Quinolyl Nitrone QN23 as a New Candidate for the Treatment of Ischemic Stroke |
| title_short | Preclinical Characterization of Antioxidant Quinolyl Nitrone QN23 as a New Candidate for the Treatment of Ischemic Stroke |
| title_sort | preclinical characterization of antioxidant quinolyl nitrone qn23 as a new candidate for the treatment of ischemic stroke |
| topic | antioxidants brain ischemia ischemic stroke neuroprotection quinolyl nitrones pharmacokinetics |
| url | https://www.mdpi.com/2076-3921/11/6/1186 |
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