Para -Substituted α-Phenyl- N - tert -butyl Nitrones: Spin-Trapping, Redox and Neuroprotective Properties

Autor: Deletraz, Anaïs, Tuccio, Béatrice, Roussel, Julien, Combes, Maud, Cohen-Solal, Catherine, Fabre, Paul-Louis, Trouillas, Patrick, Vignes, Michel, Callizot, Noelle, Durand, Grégory
Přispěvatelé: Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Radicalaire (ICR), Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Neuro-sys, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Palacky University Olomouc
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: ACS Omega
ACS Omega, 2020, 5 (48), pp.30989-30999. ⟨10.1021/acsomega.0c03907⟩
ISSN: 2470-1343
DOI: 10.1021/acsomega.0c03907⟩
Popis: International audience; In this work, a series of para-substituted α-phenyl-N-tert-butyl nitrones (PBN) were studied. Their radical-trapping properties were evaluated by electron paramagnetic resonance, with 4-CF 3-PBN being the fastest derivative to trap the hydroxymethyl radical (• CH 2 OH). The redox properties of the nitrones were further investigated by cyclic voltammetry, and 4-CF 3-PBN was the easiest to reduce and the hardest to oxidize. This is due to the presence of the electron-withdrawing CF 3 group. Very good correlations between the Hammett constants (σ p) of the substituents and both spin-trapping rates and redox potentials were observed. These correlations were further supported by computationally determined ionization potentials and atom charge densities. Finally, the neuroprotective effect of these derivatives was studied using two different in vitro models of cell death on primary cortical neurons injured by glutamate exposure or on glial cells exposed to t BuOOH. Trends between the protection afforded by the nitrones and their lipophilicity were observed. 4-CF 3-PBN was the most potent agent against t BuOOH-induced oxidative stress on glial cells, while 4-Me 2 N-PBN showed potency in both models.
Databáze: OpenAIRE
Externí odkaz: