Potential Neuroprotective Drugs in Cerebral Ischemia: New Saturated and Polyunsaturated Lipids Coupled to Hydrophilic Moieties: Synthesis and Biological Activity
| Autor: | Pamela Maher, Alain César Biraboneye, Jean-Louis Kraus, Slavica Krantic, Younes Laras, Sébastien Madonna |
|---|---|
| Přispěvatelé: | Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2009 |
| Předmět: |
Programmed cell death
Cell Survival G(M1) Ganglioside Neuroprotection Brain Ischemia Cell Line Mice Structure-Activity Relationship 03 medical and health sciences 0302 clinical medicine Drug Discovery Animals Moiety ComputingMilieux_MISCELLANEOUS 030304 developmental biology 0303 health sciences biology [CHIM.ORGA]Chemical Sciences/Organic chemistry Kinase Chemistry Glutamate receptor Brain Biological activity In vitro 3. Good health Neuroprotective Agents Biochemistry Mitogen-activated protein kinase Fatty Acids Unsaturated biology.protein Molecular Medicine Hydrophobic and Hydrophilic Interactions 030217 neurology & neurosurgery |
| Zdroj: | Journal of Medicinal Chemistry Journal of Medicinal Chemistry, 2009, 52, pp.4358-4369 Journal of Medicinal Chemistry, American Chemical Society, 2009, 52, pp.4358-4369 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm900227u |
| Popis: | The ganglioside GM1 has neuroprotective effects but is not of therapeutic value because of its lack of bioavailability. Thus, molecules that mimic GM1 represent a novel approach to neuroprotection. We have synthesized 19 small GM1-like analogues whose simplified structure includes a hydrophobic saturated or unsaturated moiety linked to a hydrophilic moiety. We report their neuroprotective effects in two distinct models of nerve cell death using hippocampus-derived HT22 cells. We found that several analogues protected the HT22 cells from death at concentrations ranging from 2 to 5 microM. Additional neuroprotective assays using cortical slices injured by glutamate confirmed these results. Since 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 GM1-like analogues. Interestingly, the results indicate that the compounds provide neuroprotection through distinct mechanisms of action. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|