微生物来源的乙酰胆碱酯酶抑制剂F99-909A的研究

F99-909 A, an acetylcholinesterase inhibitors from metabolites of microorganisms

研究利用丁酰硫代胆碱和二硫二硝基苯甲酸为底物和显色剂 ,建立一种精确、快速的高通量筛选微生物代谢产物来源的乙酰胆碱酯酶 (ACh E)抑制剂的体外筛选模型。利用此方法从 2 30 0株真菌中筛选到一株阳性菌株 F99- 90 9,该菌株的发酵液经有机溶剂提取、ODS柱层析及 HPL C制备分离 ,得到一个活性化合物 F99- 90 9A,该化合物对乙酰胆碱酯酶的 IC50 为 9.5μmol/ L。通过对该化合物的紫外、红外、质谱、核磁等理化分析 ,得知该化合物与已知化合物 radiclonic acid结构相同。但该化合物对 Ach

A rapid screening method using butylthiocholine as the substrate and dithiobisnitrobenzoate as the marker was established for screening AChE inhibitors from metabolites of microorganisms. Among the 2,300 strains of microorganisms, one culture broth designated as F99-909 was picked out as candidate with (active) principle for further isolation. The broth was processed by solvent extraction, ODS column and preparative ODS HPLC to get an active compound named F99-909A, which showed strong inhibitory activity against human AChE with IC (50) of 9.5 μmol/L. The UV, IR, MS and NMR determinations showed that F99-909 A has the same chemical structure with dradiclonic acid. It′s reported as the inhibitor of AchE for the first time.