Studies on scavenger receptor inhibitors. Part 1: synthesis and structure-activity relationships of novel derivatives of sulfatides
Autor: | Kazuya Yoshiizumi, Noriyasu Nishimura, Rika Dobashi, Fumio Nakajima, Shoji Ikeda |
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Rok vydání: | 2002 |
Předmět: |
Ceramide
Stereochemistry Arteriosclerosis Clinical Biochemistry Pharmaceutical Science Biochemistry Chemical synthesis Iodine Radioisotopes chemistry.chemical_compound Mice Structure-Activity Relationship Drug Discovery Structure–activity relationship Moiety Animals Scavenger receptor Receptors Immunologic Receptor Molecular Biology Receptors Lipoprotein Receptors Scavenger Sulfoglycosphingolipids Dose-Response Relationship Drug Macrophages Organic Chemistry Membrane Proteins Scavenger Receptors Class B In vitro Scavenger (chemistry) Lipoproteins LDL chemistry Molecular Medicine Protein Binding |
Zdroj: | Bioorganicmedicinal chemistry. 10(8) |
ISSN: | 0968-0896 |
Popis: | Scavenger receptors have been proven to be implicated in the formation of atherosclerotic lesions. A series of novel derivatives of sulfatides were synthesized, and their inhibitory activities against incorporation of DiI-acetyl-LDL into macrophages were evaluated in order to clarify the structure-activity relationships of sulfatides as a scavenger receptor inhibitor and find out novel inhibitors with synthetic easiness. The chemical modification of the substructures of sulfatides led to the establishment of the following structure-activity relationships; (1) the ceramide moiety can be replaced with another structure bearing two long chains, (2) the galactose moiety can be replaced with another structure or be deleted without a large decrease in the inhibitory activity, (3) the sulfate moiety was crucial, and it was the most preferable functional group for a potent inhibitory activity. The inhibitory activity of (S)-2-octadecanoylamino-2-tetradecylcarbamoyl)ethyl sulfate sodium salt (3a) against incorporation of DiI-acetyl-LDL into macrophages was proven to be based on the inhibition against the binding of acetyl-LDL to the surface of macrophages. We discovered novel scavenger receptor inhibitors with synthetic easiness, such as (S)-2-octadecanoylamino-2-(tetradecylcarbamoyl)ethyl sulfate sodium salt (3a) and 2-octadecanoylamino-1-(octadecanoylaminomethyl)ethyl sulfate sodium salt (13q). |
Databáze: | OpenAIRE |
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