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

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TitreCytoprotective and antioxidant properties of organic selenides for the myelin-forming cells, oligodendrocytes
Type de publicationJournal Article
Year of Publication2018
AuteursShaaban S, Vervandier-Fasseur D, Andreoletti P, Zarrouk A, Richard P, Negm A, Manolikakes G, Jacob C, Cherkaoui-Malki M
JournalBIOORGANIC CHEMISTRY
Volume80
Pagination43-56
Date PublishedOCT
Type of ArticleArticle
ISSN0045-2068
Mots-clésApoptosis, Cytoprotective, multicomponent reactions, neurodegeneration, oligodendrocytes, Organic selenides
Résumé

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.

DOI10.1016/j.bioorg.2018.05.019