Synthesis and evaluation of a difluoromethylene analogue of sphingomyelin as an inhibitor of sphingomyelinase
| Autor: | Tsutomu Yokomatsu, Hiroshi Shimeno, S. Shibuya, Takaaki Kominato, Shinji Soeda, Takeshi Akiyama, Hiroaki Takechi |
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| Rok vydání: | 2001 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Organophosphonates Pharmaceutical Science Apoptosis PC12 Cells Biochemistry Chemical synthesis Inhibitory Concentration 50 ENPP7 Microsomes Drug Discovery Animals Moiety Enzyme Inhibitors Molecular Biology Neurons biology Tumor Necrosis Factor-alpha Chemistry Organic Chemistry Brain Biological activity Rats Sphingomyelins Sphingomyelin Phosphodiesterase Enzyme inhibitor Phosphodiester bond Microsome biology.protein Molecular Medicine Cattle Sphingomyelin |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 11:1277-1280 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/s0960-894x(01)00179-2 |
| Popis: | A sphingomyelin analogue 2 , in which the long alkenyl chain and the phosphodiester moiety of sphingomyelin were replaced by a phenyl and an isosteric difluoromethylenephosphonic acid, was prepared to evaluate its inhibitory potency to sphingomyelinase. The analogue non-competitively inhibited the neutral sphingomyelinase in bovine brain microsomes with an IC 50 of 400 μM. The compound had the ability to suppress tumor necrosis factor α-induced apoptosis of PC-12 neurons at a low concentration of 0.1 μM. |
| Databáze: | OpenAIRE |
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