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

• Published in: Bioorganic chemistry 2018-10, Vol.80, p.43-56
• Main Authors: Shaaban, Saad, Vervandier-Fasseur, Dominique, Andreoletti, Pierre, Zarrouk, Amira, Richard, Philippe, Negm, Amr, Manolikakes, Georg, Jacob, Claus, Cherkaoui-Malki, Mustapha
• Format: Article
• Language: English
• Subjects: Apoptosis; Cytoprotective; Multicomponent reactions; Neurodegeneration; Oligodendrocytes; Organic selenides
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2018.05.019

Twenty-one organoselenides were synthesized and tested for their intrinsic cytotoxicity, anti-apoptotic and antioxidant capacities in oligodendrocytes. In-silico structure-activity relationship were performed to explore the drug-likeness of these organoselenides, predicting the pharmacokinetic parameters for compounds of interest that could cross the blood-brain barrier. [Display omitted] •Twenty-one organoselenides, of potential protective activity, were synthesized.•Compounds were tested for their intrinsic cytotoxicity in oligodendrocytes.•Some organoselenides showed a cytoprotective effect for oligodendrocytes.•Most of the quinone-based organoselenium showed a pro-oxidant activity.•Compounds 5b and 7b showed high glutathione peroxidase (GPx)-like activities.•Compound 5a exhibited anti-apoptotic properties in oligodendrocytes. 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.