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.
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.
Biraboneye
Alain Cesar
AC
Laboratoire de Chimie Biomoléculaire, CNRS, IBDML-UMR 6216, Campus de Luminy Case 907, Université de la Mediterranée, 13288 Marseille Cedex 090, France.
Madonna
Sebastien
S
Maher
Pamela
P
Kraus
Jean-Louis
JL
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
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