微生物来源酸性鞘磷脂酶抑制剂NF-0265A的研究

 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。

NF-0265A, an acid sphingomyelinase inhibitor from metabolites of microorganisms

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.