Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke



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Martínez-Alonso, Emma and Escobar-Peso, Alejandro and Ayuso, Maria I. and Gonzalo-Gobernado, Rafael and Chioua, Mourad and Montoya, Juan J. and Montaner, Joan and Fernández López, Israel and Marco-Contelles, José and Alcázar, Alberto (2020) Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke. Antioxidants, 9 (4). p. 291. ISSN 2076-3921

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Nitrones have a well-recognized capacity as spin-traps and are considered powerful free radical scavengers, which are two important issues in hypoxia-induced oxidative stress and cell death in brain ischemia. Consequently, nitrones have been proposed as therapeutic agents in acute ischemic stroke (AIS). In this paper, we update the biological and pharmacological characterization of ISQ-201, a previously identified cholesteronitrone hybrid with antioxidant and neuroprotective activity. This study characterizes ISQ-201 as a neuroprotective agent against the hypoxia-induced ischemic injury. Transitory four-vessel occlusion and middle cerebral artery occlusion (tMCAO) were used to induce cerebral ischemia. Functional outcomes were determined using neurofunctional tests. Infarct area, neuronal death, and apoptosis induction were evaluated. In addition, ISQ-201 reactivity towards free radicals was studied in a theoretical model. ISQ-201 significantly decreased the ischemia-induced neuronal death and apoptosis, in a dose-dependent manner, showing its therapeutic effect when administered up until 6 h after post-ischemic reperfusion onset, effects that remained after 3 months from the ischemic episode. Furthermore, ISQ-201 significantly reduced infarct volume, leading to recovery of the motor function in the tMCAO model. Finally, the theoretical study confirmed the reactivity of ISQ-201 towards hydroxyl radicals. The results reported here prompted us to suggest ISQ-201 as a promising candidate for the treatment of AIS.

Item Type:Article
Uncontrolled Keywords:antioxidant; brain ischemia; hydroxyl radical; ischemic stroke; neuroprotection; nitrones; steroids; reactive oxygen species
Subjects:Sciences > Chemistry > Chemistry, Organic
ID Code:66131
Deposited On:21 Jun 2021 14:34
Last Modified:22 Jun 2021 09:18

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