微生物来源的HLE抑制剂N01WA-735E的研究

N01WA-735E, a Human Leukocyte Elastase Inhibitor from Metabolites of Microorganisms

摘要:

人白细胞弹性蛋白酶抑制剂为筛选炎症和癌症的重要靶点。应用白细胞弹性蛋白酶抑制剂高通量的筛选模型对数千株放线菌进行筛选，发现了阳性菌株N01WA-735。首先通过形态学和化学分类学鉴定其为链霉菌属。采用有机溶剂提取、硅胶柱色谱、Sephadex LH-20柱色谱和结晶等方法对该菌株的发酵产物进行了分离纯化，得到活性单体化合物N01WA-735E，通过对N01WA-735E的理化性质和波谱数据分析，确定其结构与文献报道的化合物BE-52440A相同。该化合物对人白细胞弹性蛋白酶有很强的抑制活性，其IC50为3.02μmol/L。该化合物对人白细胞弹性蛋白酶的抑制活性国内外未见报道。

Abstract:

Human leukocyte elastase is an important selection target of inflammation and cancer. In this paper, a high throughput screening model was established for screening human leukocyte elastase inhibitors from thousands of strains of actinomycetes. As a result, a strain, N01WA-735 with potent suppression activity was isolated. Firstly, the strain N01WA-735 was identified as Streptomyces according to morphology and biochemical analysis. The Streptomyces N01WA-735 was processed by solvent extraction, silica column chromatography, Sephadex LH-20 column chromatography and crystallization to get a pure active compound named N01WA-735E. Its chemical structure was elucidated as the same as that of the compound named BE-52440A by physicochemical properties and spectral data of UV, MS, ¹H-NMR and ¹³C-NMR respectively. The compound showed a strong inhibitory activity against human leukocyte elastase with IC₅₀ of 3.02μmol/L. The compound is reported as a human leukocyte elastase inhibitor for the first time.