由一株真菌产生的抑制血管细胞粘附分子-1基因表达的活性物质的研究

Studies on a strain of fungi producing active compound that prevents VCAM-1 gene expression

以血管细胞粘附分子-1（VCAM－1）基因为靶位点，使用含有荧光素酶报告基因的转染细胞株筛选模型M-4细胞从微生物的代谢产物中高通量筛选能够抑制VCAM－1基因表达的生物活性物质，以期找到能够治疗诸如类风湿性关节炎等免疫性疾病的新型药物。在筛选过程中使用有机溶媒萃取、ODS反相柱层析、HPLC制备等方法，从真菌FO－5897的发酵液中分离到了一个对测活用细胞株的荧光素酶报告基因的表达有中等强度抑制作用的化合物，其IC50为13．8μmol／L，经各种理化性质及1H－NMR分析确定该化合物与文献报道的具有降血脂和抗癌作用的化合物Ascofuranone的结构相同。

ABSTRACT Focused on the VCAM-1 gene as the research target, we used a stable transfected cell line M-4 carrying the luciferase report gene in high throughput to screen bioactive compound that prevent the expression ofVCAM-1 from the metabolites of microorganism for the purpose of searching new drugs of treating immunological diseasessuch as rheumatoid arthritisr etc. In the course of screening, one active compound was isolated from the mycelium of astrain of fungi FO5897 by solvent extraction, ODS column chromatography and HPLC purification etc. This compoundshowed moderate inhibitory activity against the luciferase report gene expression of the assay cell line and the IC50 is13. 8μmol/L. By means of physico-chemical properties and 1H-NMR analysis, its structure of this compound was eluci-dated to be identical with the hypolipidemic and anlitumor compound ascofuranone.