Abstract
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 IC50 of 400 microM. The compound had the ability to suppress tumor necrosis factor alpha-induced apoptosis of PC-12 neurons at a low concentration of 0.1 microM.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects
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Brain
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Cattle
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology
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Inhibitory Concentration 50
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Microsomes / enzymology
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Neurons / cytology
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Neurons / drug effects
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Organophosphonates / chemical synthesis
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Organophosphonates / pharmacology
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PC12 Cells
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Rats
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Sphingomyelin Phosphodiesterase / antagonists & inhibitors*
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Sphingomyelins / chemical synthesis*
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Sphingomyelins / pharmacology
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Enzyme Inhibitors
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Organophosphonates
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Sphingomyelins
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Tumor Necrosis Factor-alpha
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Sphingomyelin Phosphodiesterase