title: Neuroprotective effects of N-alkyl-1,2,4-oxadiazolidine-3,5-diones and their corresponding synthetic intermediates N-alkylhydroxylamines and N-1-alkyl-3-carbonyl-1-hydroxyureas against in vitro cerebral ischemia.
abstract: Herein we report the synthesis and neuroprotective effects of new N-alkyl-1,2,4-oxadiazolidine-3,5-diones and their corresponding synthetic intermediates, N-alkylhydroxylamines and N-1-alkyl-3-carbonyl-1-hydroxyureas, in an in vitro model of ischemia. We found five analogues that protect HT22 cells from death in the concentration range of 1-5 muM. Because members of the MAP kinase family are known to be key players in nerve cell survival and death, we characterized the role of these kinases in the neuroprotective mechanisms of the newly synthesized analogues. The results indicate that these compounds provide neuroprotection through distinct mechanisms of action.
authors: Laboratoire de Chimie Biomoléculaire, CNRS, IBDML-UMR 6216, Campus de Luminy Case 907, Université de la Mediterranée, 13288 Marseille Cedex 090, France.
authors: Alain Cesar
authors: AC
authors: Biraboneye
authors: Sebastien
authors: S
authors: Madonna
authors: Pamela
authors: P
authors: Maher
authors: Jean-Louis
authors: JL
authors: Kraus
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006898:Hydroxylamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D006918:Hydroxyurea / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D006898:Hydroxylamines; D018696:Neuroprotective Agents; D010069:Oxadiazoles; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D006918:Hydroxyurea