41 中性スフィンゴミエリナーゼ阻害剤scyphostatinの単離・構造解析(口頭発表の部)

概要

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Ceramide, the product of sphingomyelin hydrolysis, has been reported to play an important role in signal transduction. In response to several stimuli including TNFα and IL-1β, the ceramide level increases in cells in advance of stimuli-mediated physiological and pathological processes. Thus, inhibition of sphingomyelinase(SMase) may lead to regulation of ceramide levels and to therapy for inflammation and autoimmune diseases. With this aim in mind, fermentation broths of microorganisms were screened for SMase inhibitors and scyphostatin(1) was discovered in a mycelial extract of Dasyscyphus mollissimus. The structural study of 1 was carried out by spectroscopic investigations and some chemical transformations. Then, it was established that 1 was composed of a fatty acid and an amino alchohol substituted with a highly oxygeneted cyclohexenone moiety. The structural similarity between 1 and ceramide represented by the N-acyl-amino alcohol moiety suggests that 1 may exhibit inhibitory activity as a substrate or product analogue of the enzymatic reaction. As far as we know, there are no previous reports about a neutral SMase inhibitor with significant activity, and 1 may be a useful probe for studying neutral SMase-mediated signal transduction.
天然有機化合物討論会の論文
1997-07-20