微生物来源的醛糖还原酶抑制剂F01-195A的研究

Study on F01-195A,an Aldose Reductase Inhibitor from Metabolites of Microorganisms

利用自建的高通量醛糖还原酶抑制剂的筛选方法,从数千株放线菌和真菌中筛选得到阳性菌株F01-195.对阳性菌株的发酵产物进行有机溶剂提取、硅胶柱色谱和ODS HPLC纯化,得到活性化合物F01-195A,其对醛糖还原酶有较强的特异性抑制活性,IC50为57.2μmol/L.通过对F01-195A的紫外、质谱、核磁等理化数据的分析,鉴定了其化学结构与化合物Flavomannin相同,Flavomannin已被报道作为了抗疟疾药物的先导化学物.

A high throughput screening method established by us was applied for screening aldose reductase inhibitors from thousands of strains of actinomycetes and fungi, as a result, a strain, F01-195 with the positive activity was picked out. The culture broth of the positive strain was purified by solvent extraction, silica column chromatography and ODS HPLC to get an active compound named F01-195A. The compound showed strong specific inhibitor activity against aldose reductase with IC50 of 57.2μmol/L. By the physicochemical data of UV, MS, NMR and so on, the structure of F01-195A was determined as the same as Flavomannin,which was reported as a lead compound to promising drugs against the human malaria parasite.