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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。
Using the VCAM-1 gene as a target site, high-throughput screening of M-4 cells using a transfection cell line containing a luciferase reporter gene from microbial metabolites can inhibit VCAM- 1 gene expression of bioactive substances, with a view to finding new drugs that can treat immune diseases such as rheumatoid arthritis. In the screening process using organic solvent extraction, ODS reversed-phase column chromatography, HPLC preparation and other methods, from the fungus FO-5897 fermentation broth was isolated a cell line assayed luciferase reporter gene expression with moderate inhibition The compound has an IC50 of 13.8 μmol / L. The compound has the same structure as that reported in the literature as the compound Ascofuranone which has a hypolipidemic and anti-cancer effect.