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Published on: July 31, 2017
The neuroprotective activity of 8-alkylamino-1,4-benzoxazine antioxidants
M Largeron1, B Mesples, P Gressens
1Laboratoire de Chimie Analytique et Electrochimie, Faculté des Sciences Pharmaceutiques et Biologiques, UMR 8638 CNRS-Université René Descartes, 4, Avenue de l'Observatoire, 75270 Paris Cedex 06, France. largeron@pharmacie.univ-paris5.fr
Abstract:
Antioxidant 8-alkylamino-1,4-benzoxazines, (R,S)-(3-tert-butyl-8-phenylethylamino-3,4-dihydro-2H-1,4-benzoxazin-5-yl) (phenyl) methanone (S 24429) and (R,S)-(3-cyclopentyl-8-benzylamino-3,4-dihydro-2H-1,4-benzoxazin-5-yl) (phenyl) methanone (S 24718), were prepared according to a two-step one-pot electrochemical procedure. These compounds had been selected from a previous study of structure/activity. Both compounds (1-100 microM) prevented the fall in ATP levels caused by 24 h of hypoxia in astrocytes. Both compounds (1 and 10 mg/kg i.p.) were powerful neuroprotective agents in protecting against the lesions induced by 15 microg S-bromo-willardiine injected into the cortex or white matter of 5-day old mice pups. In contrast, exifone, an antioxidant compound, was inactive at these doses. S 24429 and S 24718 appear to be novel neuroprotective agents, which are effective in a model of brain damage mimicking the lesions underlying cerebral palsy.
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