4.7 Article

Cytoprotective and antioxidant properties of organic selenides for the myelin-forming cells, oligodendrocytes

Journal

BIOORGANIC CHEMISTRY
Volume 80, Issue -, Pages 43-56

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2018.05.019

Keywords

Organic selenides; Apoptosis; Neurodegeneration; Oligodendrocytes; Multicomponent reactions; Cytoprotective

Funding

  1. Ministere des Affaires Etrangeres: the Embassy of France in Egypt-Institut Francais en Egypte
  2. Science and Technology Development Fund
  3. Conseil Regional de Bourgogne (France)
  4. Ministere de l'Enseignement et de la Recherche (France)
  5. Egyptian Ministry of Higher Education
  6. Mansoura University
  7. COST (European Cooperation in Science and Technology) [CA16112-NutRedOx]

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Here a new series of twenty-one organoselenides, of potential protective activity, were synthesized and tested for their intrinsic cytotoxicity, anti-apoptotic and antioxidant capacities in oligodendrocytes. Most of the organoselenides were able to decrease the ROS levels, revealing antioxidant properties. Compounds 5b and 7b showed a high glutathione peroxidase (GPx)-like activities, which were 1.5 folds more active than ebselen. Remarkably, compound 5a diminished the formation of the oligodendrocytes SubG1 peak in a concentration-dependent manner, indicating its anti-apoptotic properties. Furthermore, based on the SwissADME web interface, we performed an in-silico structure-activity relationship to explore the drug-likeness of these organoselenides, predicting the pharmacokinetic parameters for compounds of interest that could cross the blood-brain barrier. Collectively, we present new organoselenide compounds with cytoprotective and antioxidant properties that can be considered as promising drug candidates for myelin diseases.

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