New Biocompatible β‐Phosphorylated Linear Nitrones Targeting Mitochondria: Protective Effect in Apoptotic Cells

Autor: Marcel Culcasi, Caroline Delehedde, Mathieu Esgulian, Mathieu Cassien, Mathieu Chocry, Antal Rockenbauer, Sylvia Pietri, Sophie Thétiot‐Laurent
Přispěvatelé: Institut de Chimie Radicalaire (ICR), Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), YELEN, Institute of Materials and Environmental Chemistry [Budapest], Research Centre for Natural Sciences, Hungarian Academy of Sciences (MTA)-Hungarian Academy of Sciences (MTA), ANR-17-CE34-0006,MITODIAPM,Sondes mitochondriales et dispositifs de génération d'aérosols pour l'étude du stress oxydant et des dysfonctionnements cardiométaboliques induits par l'inhalation de faibles niveaux de particules ultrafines de pesticides chez l'animal(2017)
Rok vydání: 2023
Předmět:
Zdroj: ChemBioChem
ChemBioChem, In press, ⟨10.1002/cbic.202200749⟩
ISSN: 1439-7633
1439-4227
DOI: 10.1002/cbic.202200749
Popis: International audience; Mitochondria, an essential organelle involved in cellular respiration, energy production, and cell death, is the main cellular source of reactive oxygen species (ROS), including superoxide. Mitochondrial diseases resulting from uncontrolled/excess ROS generation are an emerging public health concern and there is current interest for specific mitochondriotropic probes to get information on in situ ROS production. As such, nitrones vectorized by the triphenylphosphonium (TPP) cation have recently drawn attention despite reported cytotoxicity. Herein, we describe the synthesis of 13 low-toxic derivatives of N-benzylidene-1-diethoxyphosphoryl-1-methylethylamine N-oxide (PPN) alkyl chain-grafted to a pyridinium, triethylammonium or berberinium lipophilic cation. These nitrones showed in vitro superoxide quenching activity and EPR/spin-trapping efficiency towards biologically relevant free radicals, including superoxide and hydroxyl radicals. Their mitochondrial penetration was confirmed by 31P NMR and anti-apoptotic properties assessed inhydrogen peroxide treated Schwann cells. Two pyridinium substituted PPNs were identified as potentially better alternatives to TPP nitrones conjugates for studies of mitochondrial oxidative damage.
Databáze: OpenAIRE
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