Synthesis and enhanced neuroprotective activity of C60-based ebselen derivatives

Abstract

A C60-based ebselen derivative 4 was synthesized through the cycloaddition of C60 with the azide (3) containing the ebselen component. It was obtained in a four-step synthesis starting from 2-(chloroseleno)benzoyl chloride and 2-(2-aminoethoxy)ethanol in 53% yield (based on consumed C60). Its structure was characterized by 1H NMR, 13C NMR, IR, UV, and FAB-MS. To verify that the C60-based ebselen derivative 4 had enhanced antioxidative and neuroprotective activity, the C60 derivative 5 and the ebselen derivative 6 were selected to treat cortical neuronal cells using the same procedures as with the C60-based ebselen derivative 4. The cellular viability of different derivative treatment groups was estimated by LDH leakage assay and MTT assay. At the same final concentration (30 µmol/L), the results showed that the antioxidative and protective potencies of the C60-based ebselen derivative 4 (MTT (OD) 0.340 ± 0.035, LDH release (UL–1) 4.80 ± 0.16) against H2O2-mediated neuronal injury have an advantage over those of C60 derivative 5 (MTT (OD) 0.297 ± 0.036, LDH release (UL–1) 5.37 ± 0.31) and ebselen derivative 6 (MTT (OD) 0.267 ± 0.027, LDH release (UL–1) 5.85 ± 0.26). Correspondingly, the GPX activity of 4 (1.62 U/µmol) was higher than that of 5 (0.77 U/µmol) and 6 (1.24 U/µmol). These findings demonstrate that the incorporation of two components with similar biological activity (C60 component and ebselen component) may be a desirable way of obtaining a new and more biologically effective C60-based compound.Key words: fullerene, ebselen derivative, azide, neuroprotective activity, cellular viability.