摘要
目的筛选信号转导相关疾病中重要靶点-酸性鞘磷脂酶抑制剂。方法使用ODS柱色谱,制备TLC和SephadexLH-20色谱等方法进行化合物的分离纯化,利用紫外、质谱等理化分析以及核磁共振等分析方法进行结构解析,利用酸性和中性SMase的活性测定方法进行活性评价。结果从微生物代谢产物的菌种中,筛选得到一个活性化合物NF-0265A,其对酸性SMase的IC50为68.7μmol·L-1。对中性SMase的活性测定的结果表明,此物质在200μmol·L-1的浓度下未见抑制作用,此化合物的化学结构与TAN-1446A的甲醇加成物相同。结论NF-0265A为第一个微生物来源的酸性SMase特异性的抑制剂,该化合物在信号转导系统和免疫系统的活性尚未见报道。
Abstract
OBJECTIVE To screen acid sphingomyelinase inhibitors from the metabolites of microorganism.METHODS The compound was isolated by ODS column chromatography, preparative TLC and Sephadex LH - 20 chromatography. The structure was identified by its physicochemical properties,13C-NMR and 1H-NMR analysis. The activity was evaluated by acid and neutral sphingomyelinase assay.RESULTS One active compound NF-0265A was isolated from the fungi NF-0265. The compound was identified to be the TAN-1466 MeOH derivate. The compound showed strong inhibitory activity against human acid sphingomyelinase with the IC50 of 68.7μmol·L-1 ,but no inhibitory against neutral sphingomyelinase at the concentration of 200 μmol·L-1 .CONCLUSION NF-0265A is the specific acid sphingomyelinase inhibitor from the metabolites of microorganisms which was firstly reported this time.
关键词
酸性鞘磷脂酶 /
抑制剂 /
NF-0265A
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Key words
acid sphingomyelinase /
inhibitor /
NF-0265A
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董悦生;杨峻山;张华;贺建功.
微生物来源酸性鞘磷脂酶抑制剂NF-0265A的研究[J]. 中国药学杂志, 2005, 39(22): 1752-1754
DONG Yue-sheng;YNG Jun-shn;ZHNG Hu;HE Jin-gong.
NF-0265A, an acid sphingomyelinase inhibitor from metabolites of microorganisms [J]. Chinese Pharmaceutical Journal, 2005, 39(22): 1752-1754
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参考文献
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脚注
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