C60-based ebselen derivative: Synthesis by bingel cyclopropanation and enhanced antioxidative and neuroprotective activity

Abstract

C60-based ebselen derivative 3 was synthesized through Bingel cyclopropanation of C60 with the ebselen malonate 2. Compound 3 was obtained in 42% yield (based on consumed C60) in a three-step synthesis starting from 2-(chloroseleno)benzoyl chloride and 2-(2-aminoethoxy)ethanol. Its structure was confirmed by 1H NMR, 13C NMR, IR, UV and FAB-MS spectroscopy analyses. In order to verify the enhanced antioxidative and neuroprotective activity of 3, a C60 derivative (4), an ebselen derivative (2), and their mixture (4 plus 2 in equimolar ratio) were employed to treat cortical neuronal cells, following the same procedure used with 3 and at the same final concentration (30 μmol L-1). Cell viabilities of the four treated groups were estimated by LDH (lactic dehydrogenase) leakage and MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5- diphenyl-tetrazolium bromide) assays. Results showed that the antioxidative and protective activities of C60-based ebselen derivative 3 against H2O2-mediated neuronal injury (MTT(OD) 0.364 ± 0.028; LDH release (UL-1) 4.66 ± 0.28) were significantly higher than those of C60 derivative 4 (MTT(OD) 0.324 ± 0.025; LDH release (UL-1) 5.39 ± 0.17), ebselen derivative 2 (MTT(OD) 0.294 ± 0.021; LDH release (UL-1) 5.71 ± 0.27), and the mixture of 4 and 2 (MTT(OD) 0.310 ± 0.018; LDH release (UL-1) 5.54 ± 0.39). These findings demonstrated that the combination of two molecular units with similar biological activities (C60 and ebselen) may be a desirable way of obtaining new and more biologically effective C 60-based compounds. ©2007 Sociedade Brasileira de Química.